IJO International Journal of Oncology 1019-6439 1791-2423 D.A. Spandidos 10.3892/ijo.2012.1744 ijo-42-02-0478 Articles Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis KOMATSUMASATO12* YOSHIMARUTETSURO1* MATSUOTAISUKE1 KIYOTANIKAZUMA1 MIYOSHIYASUO3 TANAHASHITOSHIHITO4 ROKUTANKAZUHITO4 YAMAGUCHIRUI5 SAITOAYUMU6 IMOTOSEIYA6 MIYANOSATORU6 NAKAMURAYUSUKE7 SASAMITSUNORI8 SHIMADAMITSUO2 KATAGIRITOYOMASA1 Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Hyogo 663-8501; Department of Digestive and Transplantation Surgery, The University of Tokushima Graduate School, Hyogo 663-8501; Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Hyogo 663-8501; Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503; Laboratories of Sequence Analysis, The University of Tokyo, Tokyo 108-8639; DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639; Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639; Tokushima Breast Care Clinic, Tokushima 770-0052, Japan Correspondence to: Dr Toyomasa Katagiri, Division of Genome Medicine, Institute of Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan, E-mail: tkatagi@genome.tokushima-u.ac.jp

Contributed equally

 2 2013 18 12 2012 42 2 478 506 22 09 2012 06 11 2012 Copyright © 2013, Spandidos Publications 2013 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify the molecular mechanisms involved in the carcinogenesis of TNBC and to identify target molecules for novel anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 and 321 transcripts that were significantly upregulated and downregulated in TNBC, respectively. In particular, gene expression profile analyses of normal human vital organs allowed us to identify 104 cancer-specific genes, including those involved in breast carcinogenesis such as NEK2, PBK and MELK. Moreover, gene annotation enrichment analysis revealed prominent gene subsets involved in the cell cycle, especially mitosis. Therefore, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly-associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC. Small-interfering RNA-mediated knockdown of their expression significantly attenuated TNBC cell viability due to G1 and G2/M cell cycle arrest. Our data will provide a better understanding of the carcinogenesis of TNBC and could contribute to the development of molecular targets as a treatment for TNBC patients.

 triple negative breast cancer expression profiling molecular targets Introduction

Breast cancer is one of the most common solid malignant tumors among women worldwide. Breast cancer is a heterogeneous disease that is currently classified based on the expression of estrogen receptor (ER), progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER2) (1,2). For patients with ER- or PgR-positive breast cancer, approximately five years of adjuvant endocrine therapy reduces the annual breast cancer death rate by approximately 30% (3). The addition of HER2-antagonist trastuzumab to adjuvant chemotherapy has improved the prognosis of HER2-positive breast cancer patients (4–6). In contrast, triple negative breast cancer (TNBC), defined as tumors that are negative for ER, PgR and HER2 overexpression, accounts for at least 15–20% of all breast cancers, and the prognosis for TNBC patients is poor because of its propensity for recurrence and metastasis and a lack of clinically-established targeted therapies (7,8). Therefore, only neoadjuvant chemotherapy with conventional cytotoxic agents yield an excellent outcome for TNBC patients who have a complete pathological response, but the outcome for the vast majority with residual disease after chemotherapy is relatively poor compared to non-TNBC patients (6,7). Thus, because the heterogeneity of breast cancer makes it difficult to treat many subtypes, including TNBC, the molecular mechanisms of the carcinogenesis of TNBC must be elucidated to develop novel molecular-targeted therapies that improve the clinical outcome of TNBC patients.

Current ‘omics’ technology including DNA microarray analysis can provide very helpful information that can be used to categorize the characteristics of various malignant tumors and identify genes that may be applicable for the development of novel molecular targets for therapeutic modalities (9). To this end, we analyzed the gene expression profile of 30 TNBC cells and normal breast ductal cells that were purified by laser-microbeam microdissection and identified a number of cancer-specific genes that might contribute to the carcino genesis of TNBC. TNBC gene expression profiling analysis can provide comprehensive information on the molecular mechanism underlying the carcinogenesis of TNBC and possibly lead to the development of novel effective therapies.

 Materials and methods Clinical samples and cell lines

A total of 48 TNBC (18 cases did not entry DNA microarray analysis) and 13 normal mammary tissues were obtained with informed consent from patients who were treated at Tokushima Breast Care Clinic, Tokushima, Japan. This study, as well as the use of all clinical materials described above, was approved by the Ethics Committee of The University of Tokushima. Clinical information was obtained from medical records and tumors were diagnosed as triple-negative by pathologists when immunohistochemical staining was ER-negative, PR-negative, and HER2 (0 or 1+). The clinicopathological features of each patient are summarized in Table I. Samples were immediately embedded in TissueTek OCT compound (Sakura, Tokyo, Japan), frozen, and stored at −80°C. Human TNBC cell lines MDA-MB-231, BT-20, BT-549, HCC1143, and HCC1937 were purchased from the American Type Culture Collection (ATCC, Rockville, MD, USA). The human normal breast epithelial cell line, MCF10A, was purchased from Cambrex Bioscience, Inc. All cells were cultured under the conditions recommended by their respective depositors.

 Laser-microbeam microdissection (LMM), RNA extraction, RNA amplification, and hybridization

Frozen specimens were serially sectioned in 8-μm slices with a cryostat (Leica, Herborn, Germany) and stained with hematoxylin and eosin to define the analyzed regions. We purified 48 TNBC and 13 normal ductal cells using the LMM system (Carl Zeiss, Jena, Germany) according to the manufacturer’s instructions. Dissected cancer and normal ductal cells were dissolved in RLT lysis buffer (Qiagen, Valencia, CA, USA) containing 1% β-mercaptoethanol. The extracted total RNA was purified with an RNeasy Mini kit (Qiagen) according to the manufacturer’s instructions. For RNA amplification and labeling, we used an Agilent Low-Input QuickAmp labeling kit according to the manufacturer’s instructions. Briefly, 100 ng of total RNA from each sample was amplified using T7 RNA polymerase with simultaneous Cy3-labeled CTP incorporation. Then, 2 μg of Cy3-labeled cRNA was fragmented, hybridized onto the Agilent Whole Human Genome Microarray 4×44K slide (Agilent Technologies, Palo Alto, CA, USA) and then incubated with rotation at 65°C for 18 h. Then slides were washed and scanned by the Agilent Microarray scanner system in an ozone protection fume hood.

 Microarray analysis

The features of scanned image files containing the Cy3-fluorescence signals of the hybridized Agilent Microarrays were extracted using the Agilent Feature Extraction (version 9.5) (Agilent Technologies). The data were analyzed using GeneSpring (version 11.5). We normalized the microarray data across all chips and genes by quantile normalization, and baseline transformed the signal values to the median in all samples. Finally, we performed quality control and filtering steps based on flags and expression levels. To identify genes that were significantly alternated between TNBC and normal ductal cells the mean signal intensity values in each analysis were compared. In this experiment, we applied Mann-Whitney (unpaired) t-test and random permutation test 10,000 times for each comparison and adjusted for multiple comparisons using the Benjamini Hochberg false discovery rate (FDR). Gene expression levels were considered significantly different when the FDR (corrected P-value) <5×10−4 (when comparing normal ductal cells and TNBC) and the fold change was ≥5.0. Data from this microarray analysis has been submitted to the NCBI Gene Expression Omnibus (GEO) archive as series GSE38959.

 Functional gene annotation clustering

The Database for Annotation, Visualization and Integrated Discovery (DAVID 6.7) was approved to detect functional gene annotation clusters based on gene expression profiling by gene annotation enrichment analysis (http://david.abcc.ncifcrf.gov/) (10,11). The clusters from the gene annotation enrichment analysis were selected in this study based on a previous report (12).

 Quantitative reverse transcription-PCR (qRT-PCR) analysis

Total RNA was extracted from each TNBC cell line and clinical sample using an RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. Purified RNA from each clinical sample and cell line, as well as poly-A RNA from normal human heart, lung, liver, and kidney (Takara, Otsu, Japan) was reverse transcribed for single-stranded cDNA using oligo(dT)12–18 primers with Superscript II reverse transcriptase (Invitrogen, Life Technologies, Carlsbad, CA, USA). qRT-PCR analysis was performed using an ABI PRISM 7500 Real-Time PCR system (Applied Biosystems, Life Technologies, Carlsbad, CA, USA) and SYBR Premix Ex Taq (Takara) according to the manufacturer’s instructions. The PCR primer sequences were as follows: 5′-GCAGGTCTCC TTTCCTTTGCT-3′ and 5′-CTCGGCCTTCTTTGAGT GGT-3′ for ASPM; 5′-CACTCACCGATTCAAATG CTC-3′ and 5′-ACCACCGTTGTTCCCTTTCT-3′ for CENPK; 5′-AAC TTAGAGGTGGGGAGCAG-3′ and 5′-CACAACCATGCC TTACTTTATC-3′ for β2 microglobulin (β2-MG) as a quantitative control.

 Gene-silencing effect by RNA interference

Targeted sequences for ASPM and CENPK were determined using an siRNA Targeted Finder (Applied Biosystems, Life Technologies; http://www.ambion.com/techlib/misc/siRNA_finder.html). The siRNA targeting sequences were 5′-CATACAGAAGT GCGAGAAA-3′ for ASPM, 5′-CTCAGTCAATGGC AGAAAA-3′ for CENPK and 5′-GCAGCACGACTTCT TCAAG-3′ for EGFP as a control siRNA. Human TNBC cell lines, HCC1937, MDA-MB-231 and BT-20, were plated at a density of 1×104 cells per well in 12-wells for the MTT assay and 3×104 cells per well in 6-well plates for flow cytometry and RT-PCR analyses. Cells were transfected with 16.6 nM of each siRNA using Lipofectamine RNAiMAX Reagent (Invitrogen). To evaluate the gene-silencing effects of the siRNAs by qRT-PCR, total RNA was extracted from the siRNA-transfected cells as described above after the indicated times. The following specific qRT-PCR primer sets were used: 5′-CGGAAAAGAAAGAGCGATGG-3′ and 5′-ACCACCAAGTGAAGCCCTGT-3′ for ASPM and 5′-GG GTGCCATCATTTTCTGGT-3′ and 5′-CCACCGTTGTT CCCTTTCTAAG-3′ for CENPK. To evaluate cell viability, the MTT assay was performed using the cell counting kit-8 reagent (Dojindo, Kumamoto, Japan) according to the manufacturer’s instructions. Absorbance at 450 nm was measured with a micro-plate reader infinite 200 (Tecan, Männedorf, Switzerland). These experiments were performed in triplicate.

 Colony formation assay

Vector-based shRNAs and the psiU6BX3 expression system were constructed as previously described (13). The shRNA target sequences were the same as those of the siRNA oligonucleotides. The DNA sequences of all constructs were confirmed by DNA sequencing. BT-20 and MDA-MB-231 cells were plated in 10-cm dishes (1×106 cells/dish) and transfected with 6 μg of psiU6BX3.0-ASPM or psiU6BX3.0-CENPK and psiU6BX3.0-EGFP as a control using Fugene-6 (Roche, Basel, Switzerland) according to the manufacturer’s instructions. Forty-eight hours after transfection, cells were re-seeded for a colony formation assay (5.0×105 cells/10-cm dish) and RT-PCR (5.0×105 cells/10-cm dish). We selected psiU6BX3.0-transfected cells using selection medium containing 0.6 mg/ml of neomycin for BT-20 cells and 1.4 mg/ml for MDA-MB-231 cells. Total RNA was extracted from the cells after a 7-day incubation with neomycin, and then the knockdown effects of the siRNAs were examined by qRT-PCR. The specific primer sets for quantitative RT-PCR were the same as those for the siRNA oligonucleotides. Nineteen days after transfection, the cells were fixed with 4% paraformaldehyde for 10 min and stained with Giemsa solution (Merck, Darmstadt, Germany).

 Cell cycle analysis

For flow cytometric analysis, adherent and detached cells were harvested and fixed with 70% ethanol at room temperature for 30 min. After washing with PBS (−), the cells were incubated at 37°C for 30 min with 1 mg/ml RNase I in PBS (−) and stained with 20 μg propidium iodide at room temperature for 30 min in the dark. A total of 10,000 cells were analyzed for DNA content using flow cytometry and CellQuest software (FACSCalibur; BD Biosciences, Franklin Lakes, NJ, USA). Assays were performed in duplicate.

 Immunocytochemical staining analysis

HCC1937 and MDA-MB-231 cells were plated onto a 2-well glass slide (Thermo Fisher Scientific, Rochester, NY, USA) at a density of 1.0×104/well and incubated for 24 h before siRNA trans fection. Forty-eight hours post-transfection, the cells were fixed with 4% paraformaldehyde for 30 min at 4°C and then permeablized with 0.1% Triton X-100 for 2 min at room temperature. Subsequently, the cells were covered with 3% bovine serum albumin for 60 min at room temperature and then incubated with an anti-α/β tubulin antibody (Cell Signaling, Beverly, MA, USA) diluted 1:50 for 1 h. After washing with PBS (−), the cells were stained with an Alexa 488-conjugated anti-rabbit secondary antibody (Molecular Probes, Eugene, OR, USA) diluted 1:1,000 for 1 h. The nuclei were counterstained with 4′,6′-diamidine-2′-phenylindole dihydrochloride (DAPI). Fluorescent images were obtained using an IX71 microscope (Olympus, Tokyo, Japan).

 Statistical analysis

Statistical significance was calculated by Mann-Whitney t-test using Stat View 5.0 J software (SAS Institute, Inc., Cary, NC, USA) to compare the gene expression levels between TNBC cells and normal ductal cells, and by Student’s two-sided t-test using Microsoft® Excel 2008 to assess cell proliferation, gene expression, and alteration of cell cycle. A difference of P<0.05 was considered statistically significant.

 Results Identification of genes upregulated or downregulated in TNBCs

To obtain precise expression profiles of TNBC cells, we used LMM to avoid contamination of non-cancer cells, such as adipocytes, fibroblasts, and inflammatory cells from the tissue sections (Fig. 1A, upper panels). Because breast cancer originates from normal breast ductal cells, we used similarly purified populations of normal duct cells as controls (Fig. 1A, lower panels). The precise gene-expression profiles of TNBC by DNA microarray identified 301 genes that were upregulated >5-fold in TNBC compared to 13 normal ductal cells, and 321 genes that were downregulated to <1/5 of the normal ductal cells (Fig. 1B). Table II lists the 301 upregulated genes in TNBC, including ubiquitin-conjugating enzyme E2C (UBE2C) (14), S100 calcium binding protein P (S100P) (15), ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) (UCHL1) (16), pituitary tumor-transforming 1 (PTTG1) (17), ubiquitinconjugating enzyme E2T (UBE2T) (13), ubiquitin-like with PHD and ring finger domains 1 (UHRF1) (18), SIX homeobox 1 (SIX1) (19), and protein regulator of cytokinesis 1 (PRC1) (20), which were previously reported to be overexpressed in breast cancer and involved in mammary carcinogenesis. In particular, topoisomerase (DNA) IIα (TOP2A) (21,22), HORMA domain containing 1 (HORMAD1) (23), ATPase family, Fatty acid binding protein 5 (psoriasis-associated) (FABP5) (24), and AAA domain containing 2 (ATAD2) (25) were previously reported to be potentially involved in the carcinogenesis of TNBC, and to serve as prognostic markers or therapeutic targets for TNBC.

On the other hand, Table III lists the 321 genes that were downregulated to <1/5 of normal ductal cells. Among these significantly downregulated genes, prolactin-induced protein (PIP) and dynein, axonemal, light intermediate chain 1 (DNALI1) were previously shown to be downregulated in TNBC (26). In particular, suppression of WNT inhibitory factor 1 (WIF1) (27) and signal peptide, CUB domain, EGF-like (SCUBE2) (28), both of which function as tumor suppressors, were among the genes that were downregulated as malignancy progressed. These data suggest that silencing or depletion of these genes might lead to the carcinogenesis of TNBC.

 Identification of cancer-specific genes

Next, to develop novel therapeutic targets for TNBC with a minimum risk of adverse events, we performed a DNA microarray analysis of normal human vital organs consisting of the heart, lung, liver and kidney as well as TNBC cases and attempted to identify genes whose expression was exclusively upregulated in TNBC, but not expressed in normal vital organs. We identified 104 genes, which were specifically upregulated in TNBC, including cancer-specific molecules such as NIMA-related kinase 2 (NEK2) (29,30), PDZ binding kinase (PBK) (31), denticleless homolog (Drosohila) (DTL) (32), maternal leucine zipper kinase (MELK) (33), and kinesin family member C (KIF2C) (34), which have previously been shown to be involved in breast carcinogenesis (Fig. 1C and Table IV).

 Functional gene annotation clustering analysis

To elucidate the biological processes and pathways characterized in TNBC, we performed a functional analysis of these upregulated or downregulated genes in 30 TNBC cases using the gene annotation clustering of the DAVID algorithm. We identified the most prominent cluster (cluster 1; gene enrichment score, 29.90) composed of various functional annotation terms consisting of 87 upregulated genes in TNBC (Table V). Cluster 1 consisted almost entirely of cell cycle-associated genes as represented by nuclear division (fold enrichment, 15.04), mitosis (fold enrichment, 15.04), M phase of the mitotic cell cycle (fold enrichment, 14.78), organelle fission (fold enrichment, 14.45), and M phase (fold enrichment, 12.90) (Fig. 2). These findings suggest that most of the upregulated genes in TNBC might be functionally responsible for cell cycle progression.

On the other hand, we also identified the most prominent cluster functionally deactivated in TNBC based on down-regulated genes in TNBC (cluster 2; enrichment score, 6.43). As shown in Table V and Fig. 2, cluster 2 consisted of functions induced by extracellular matrix-cell adhesion-associated genes such as latent transforming growth factor β binding protein 2 (LTBP2), laminin α3 (LAMA3) and cell adhesion molecule with homology to L1CAM (close homolog of L1) (CHL1), which have been reported to be downregulated in various tumors (35–37). These results suggest that loss of cell-cell or matrix-cell interactions might be a key mechanism in TNBC progression.

 Identification of ASPM and CENPK as novel molecular targets for TNBC therapy

Because the upregulated genes were mainly included in the cell cycle-associated gene cluster as described above, we directed our focus to two cancer-specific genes that function as cell cycle regulators, asp (abnormal spindle) homolog, microcephaly associated (Drosophila) (ASPM), which is fundamental for cytokinesis (38) and centromere protein K (CENPK), which is essential for proper kinetochore assembly during mitosis (39), as novel therapeutic targets for TNBC. qRT-PCR experiments confirmed that ASPM and CENPK genes were significantly upregulated in 48 clinical TNBC cases (Fig. 3A) and five cell lines derived from TNBC (Fig. 3B), but undetectably expressed in a mixture of 13 microdissected normal mammary ductal cells and the normal mammary epithelial cell line MCF10A as well as normal human vital organs.

To ascertain the possible roles of ASPM and CENPK in TNBC cell growth, we knocked down the expression of endogenous ASPM and CENPK in three TNBC cell lines, HCC1937, BT-20 and MDA-MB-231 cells, which highly express both of these genes (Fig. 3), using RNAi. qRT-PCR experiments showed that ASPM and CENPK were significantly knocked down in cells transfected with siASPM and siCENPK, but not with siEGFP as a control (Fig. 4A). In concordance with their knockdown, the MTT assay clearly revealed growth suppression of breast cancer cells in a time-dependent manner by siASPM and siCENPK, compared with a control siEGFP, which showed no knockdown (Fig. 4B). In addition, a colony formation assay also confirmed that introducing both shRNA-ASPM and -CENPK constructs remarkably suppressed the growth of BT-20 and MDA-MB-231 cells, respectively, compared with shEGFP-transfected cells (Fig. 4C), suggesting that both genes are likely indispensable for breast cancer cell growth. Furthermore, we investigated the phenotypic alterations of TNBC cells transfected with ASPM and CENPK siRNAs showing significant knockdown effects. FACS analysis revealed that depleting ASPM caused a cell cycle arrest at the G2/M phase in HCC1937 cells (siEGFP:siASPM, 24.4:34.0%) at 2 days after transfection, and a subsequent increase in the sub-G1 population (siEGFP:siASPM, 9.86:43.68%) at 6 days (Fig. 5A). On the other hand, reduced CENPK expression resulted in an increase in the proportion of G0/G1 phase cells (siEGFP:siCENPK, 56.49:72.2%) in MDA-MB-231 after 2 days of transfection, and a subsequent increase in the sub-G1 population (siEGFP:siCENPK, 12.73:30.96%) at 6 days (Fig. 5B). Interestingly, we observed an enlarged size of HCC1937 cells, which was likely due to abnormal tubulin formation due to decreased ASPM expression (Fig. 5C, arrowheads). In addition, we observed a disruption in the structural integrity of tubulin in CENPK-depleted MDA-MB-231 cells (Fig. 5D, arrowheads), compared with those in siEGFP-transfected cells.

These results suggest that the absence of ASPM and CENPK caused an arrest in the G2/M and G0/G1 phases, respectively, and then induced cell death. Taken together, these findings strongly suggest that ASPM and CENPK have indispensable roles in cell proliferation and mitosis, especially in the G2/M and G0/G1 phases, in TNBC cells.

 Discussion

TNBC patients do not benefit from endocrine therapy and trastuzumab. Conventional chemotherapy is currently the mainstay of systemic medical treatment, although TNBC patients have a worse outcome after chemotherapy than patients with other breast subtypes. In particular, because cytotoxic drugs often cause severe adverse effects, it is obvious that thoughtful selection of novel target molecules based on the detailed molecular mechanisms of TNBC carcinogenesis should be very helpful to develop effective anticancer drugs with a minimum risk of side effects. To this end, we performed DNA microarray using the microdissected TNBC and normal ductal cells, and normal human vital organs including the heart, lung, liver and kidney and identified 104 genes that were significantly upregulated in TNBC compared to normal duct cells, but not expressed in normal human vital organs. They included cancer specific kinases, such as NEK2, PBK, and MELK, which might serve as druggable targets for new therapeutic agents against TNBC.

NEK2, a member of the NIMA-related serine/threonine kinase family, is involved in cell division and the mitotic regulation by centrosome splitting, and is upregulated in a wide variety of human cancers including breast cancer (40). siRNA-mediated depletion of NEK2 expression results in growth suppression of breast and colorectal cancers (29,30). PBK, a mitotic serine/threonine kinase, is significantly upregulated in the majority of breast cancers. siRNA-mediated knockdown of PBK expression also results in significant suppression of cell growth due to cytokinetic failure (31). MELK, a member of the snf1/AMPK serine-threonine kinase family, is involved in mammalian embryonic development and is also frequently upregulated in breast cancers and brain tumors (33,41). Suppression of MELK expression by siRNA significantly inhibits the growth of human breast cancer cells (33). These findings strongly suggest that these cancer-specific kinases, NEK2, PBK and MELK, are promising therapeutic targets for TNBC.

Furthermore, we performed a gene-annotation enrichment analysis using DAVID based on gene expression profiling to elucidate the biological processes and pathways associated with each gene cluster. We found that the vast majority of genes upregulated in TNBC are functionally responsible for cell cycle progression involved in nuclear division, microtubule organization, kinetochore, and chromosome segregation, and that most inactivated functions closely related to TNBC progression are involved in cell-cell or cell-matrix interactions, which is consistent with epithelial mesenchymal transition (EMT) features as a phenotype of TNBC (42).

To further the development of novel anticancer drugs with minimum adverse effects, we focused on the cancer-specific cell-cycle associated genes ASPM and CEPNK as novel molecular targets for TNBC therapy. ASPM has been reported to play an essential role in nucleating microtubules at centrosomes, to localize to the spindle poles during mitosis (39) and to contribute to glioblastoma cell growth (43), but has not been associated with breast carcinogenesis, especially TNBC. Here, we confirmed that ASPM is upregulated in clinical samples and TNBC cell lines (Fig. 3) and that siRNA-mediated knockdown of endogenous ASPM results in the loss of nucleating microtubules through mitosis by impeding centrosome function, resulting in G2/M cell cycle arrest and subsequent apoptosis. These results suggest that aberrant ASPM expression might be involved in the carcinogenesis of TNBC and that ASPM targeting might be an attractive therapeutic option with less adverse effects. CENPK is known to be a subunit of the CENPH-I complex, and essential for proper kinetochore assembly (39), but little is known about the roles of CENPK in human cancer growth, progression, and carcinogenesis. We also confirmed that CENPK is upregulated in clinical samples and TNBC cell lines, and that siRNA-mediated knockdown also causes cell growth inhibition through G0/G1 cell cycle arrest due to a loss of correct tubulin structures (Figs. 3–5). Interestingly, we determined that other centromere or kinetochore-associated proteins, CENPA, CENPF, CENPI, CENPM, NDC80 and HJURP, were also significantly overexpressed in TNBC cases, but not expressed in normal vital organs (Fig. 1C and Table IV). Human CENPA was first identified based on autoantibodies found in patients suffering from scleroderma (44) and is over-expressed in colorectal cancers (45). CENPF is also reportedly upregulated in head and neck squamous cell carcinomas and pancreatic ductal carcinomas (46,47). NDC80 and HJURP are reportedly overexpressed in breast cancers and associated with tumor grade and poor prognosis (48,49). These findings suggest that aberrant regulation of kinetochore assembly and centromere function through mitosis might contribute to the carcinogenesis of TNBC and that destroying one component of the kinetochore, such as targeting CENPK, might be a novel molecular target for TNBC treatment.

TNBC is a heterogeneous subgroup of breast cancers; therefore oncologists, pathologists, and geneticists had tried to clarify TNBC by means of gene expression profiling and immunohistochemical analyses. We also applied unsupervised 2-dimensional hierarchical clustering analysis to groups of genes based on similarities in the expression pattern, but there is no clustering for TNBC based on gene expression patterns, probably due to the small sample size (data not shown). However, the information provided in this study will facilitate the development of novel and attractive molecular drug targets without adverse events.

We thank Dr Tomoya Fukawa and Dr Le Tan Dat for helpful and constructive discussions and Ms. Hitomi Kawakami for technical assistance in microdissection. This work was supported in part by a grant from Health Labour Research Grant ‘Third Term Comprehensive Control Research for Cancer (H24-3rd-Gan-Ippan-006), and Kobayashi Foundation for cancer Research (2009) (TK).

 References JemalASiegelRWardEHaoYXuJMurrayTThunMJCancer Statistics, 2008CA Cancer J Clin5871962008 Di CosimoSBaselgaJManagement breast cancer with targeted agents: importance of heterogeneityNat Rev Clin Oncol71391472010 RahmanMPumphreyJGLipkowitzSThe TRAIL to targeted therapy of breast cancerAdv Cancer Res10343732009 SmithIProcterMGelberRDGuillaumeSFeyereislovaADowsettMGoldhirschAUntchMMarianiGBaselgaJKaufmannMCameronDBellRBerghJColemanRWardleyAHarbeckNLopezRIMallmannPGelmonKWilckenNWistESánchez RoviraPPiccart-GebhartMJHERA study team: 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trialLancet36929362007 RomondEHPerezEABryantJSumanVJGeyerCEJrDavidsonNETan-ChiuEMartinoSPaikSKaufmanPASwainSMPisanskyTMFehrenbacherLKuttehLAVogelVGVisscherDWYothersGJenkinsRBBrownAMDakhilSRMamounasEPLingleWLKleinPMIngleJNWolmarkNTrastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancerN Engl J Med353167316842005 JoensuuHKellokumpu-LehtinenPLBonoPAlankoTKatajaVAsolaRUtriainenTKokkoRHemminkiATarkkanenMTurpeenniemi-HujanenTJyrkkiöSFlanderMHelleLIngalsuoSJohanssonKJääskeläinenASPajunenMRauhalaMKaleva-KerolaJSalminenTLeinonenMElomaaIIsolaJfor the FinHer Study InvestigatorsAdjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancerN Engl J Med3548098202006 FoulkesWDSmithIEReis-FilhoJSTriple-negative breast cancerN Engl J Med363193819482010 LiedtkeCMazouniCHessKRAndréFTordaiAMejiaJASymmansWFGonzalez-AnguloAMHennessyBGreenMCristofanilliMHortobagyiGNPusztaiLResponse to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancerJ Clin Oncol26127512812008 PetricoinEFIIIHackettJLLeskoLJPuriRKGutmanSIChumakovKWoodcockJFeigalDWJrZoonKCSistareFDMedical applications of microarray technologies: a regulatory science perspectiveNat Genet324744792002 HuangDWShermanBTLempickiRASystematic and integrative analysis of large gene lists using DAVID Bioinformatics ResourcesNat Protoc444572009 HuangDWShermanBTLempickiRABioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene listsNucleic Acids Res371132009 HaoJMChenJZSuiHMSi-MaXQLiGQLiuCLiJLDingYQLiJMA five-gene signature as a potential predictor of metastasis and survival in colorectal cancerJ Pathol2204754892010 UekiTParkJHNishidateTKijimaKHirataKNakamuraYKatagiriTUbiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cellsCancer Res69875287602009 LoussouarnDCampionLLeclairFCamponeMCharbonnelCRicolleauGGouraudWBatailleRJézéquelPValidation of UBE2C protein as a prognostic marker in node-positive breast cancerBr J Cancer1011661732009 ArumugamTLogsdonCDS100P: a novel therapeutic target for cancerAmino Acids418938992011 XiangTLiLYinXYuanCTanCSuXXiongLPuttiTCOberstMKellyKRenGTaoQThe ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancerPLoS One7e297832012 YoonCHKimMJLeeHKimRKLimEJYooKCLeeGHCuiYHOhYSGyeMCLeeYYParkICAnSHwangSGParkMJSuhYLeeSJPTTG1 oncogene promotes tumor malignancy via epithelial to mesenchymal transition and expansion of cancer stem cell populationJ Biol Chem28719516195272012 JinWLiuYXuSGYinWJLiJJYangJMShaoZMUHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to anticancer drugsBreast Cancer Res Treat12439482010 FordHLLandesman-BollagEDacwagCSStukenbergPTPardeeABSeldinDCCell cycle-regulated phosphorylation of the human SIX1 homeodomain proteinJ Biol Chem27522245222542000 ShimoANishidateTOhtaTFukudaMNakamuraYKatagiriTElevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cellsCancer Sci981741812007 Di LeoAIsolaJTopoisomerase II alpha as a marker predicting the efficacy of anthracyclines in breast cancer: are we at the end of the beginning?Clin Breast Cancer41791862003 NakagawaMBandoYNagaoTMorimotoMTakaiCOhnishiTHondaJMoriyaTIzumiKTakahashiMSasaMTangokuAExpression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancerAnticancer Res31238923932011 AdélaïdeJFinettiPBekhoucheIRepelliniLGeneixJSircoulombFCharafe-JauffretECerveraNDesplansJParzyDSchoenmakersEViensPJacquemierJBirnbaumDBertucciFChaffanetMIntegrated profiling of basal and luminal breast cancersCancer Res6711565115752007 LiuRZGrahamKGlubrechtDDGermainDRMackeyJRGodboutRAssociation of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapyAm J Pathol17899710082011 KalashnikovaEVRevenkoASGemoATAndrewsNPTepperCGZouJXCardiffRDBorowskyADChenHWANCCA/ATAD2 overexpression identifies breast cancer patients with poor prognosis, acting to drive proliferation and survival of triple-negative cells through control of B-Myb and EZH2Cancer Res70940294122010 ParrisTZDanielssonANemesSKovácsADelleUFalleniusGMöllerströmEKarlssonPHelouKClinical implications of gene dosage and gene expression patterns in diploid breast carcinomaClin Cancer Res16386038742010 AiLTaoQZhongSFieldsCRKimWJLeeMWCuiYBrownKDRobertsonKDInactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancerCarcinogenesis27134113482006 ChengCJLinYCTsaiMTChenCSHsiehMCChenCLYangRBSCUBE2 suppresses breast tumor cell proliferation and confers a favorable prognosis in invasive breast cancerCancer Res69363436412009 TsunodaNKokuryoTOdaKSengaTYokoyamaYNaginoMNimuraYHamaguchiMNek2 as a novel molecular target for the treatment of breast carcinomaCancer Sci1001111162009 SuzukiKKokuryoTSengaTYokoyamaYNaginoMHamaguchiMNovel combination treatment for colorectal cancer using Nek2 siRNA and cisplatinCancer Sci101116311692010 ParkJHLinMLNishidateTNakamuraYKatagiriTPDZ-binding kinase/T-LAK cell-originated protein kinase, a putative cancer/testis antigen with an oncogenic activity in breast cancerCancer Res66918691952006 UekiTNishidateTParkJHLinMLShimoAHirataKNakamuraYKatagiriTInvolvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cellsOncogene27567256832008 LinMLParkJHNishidateTNakamuraYKatagiriTInvolvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 familyBreast Cancer Res9R172007 ShimoATanikawaCNishidateTLinMLMatsudaKParkJHUekiTOhtaTHirataKFukudaMNakamuraYKatagiriTInvolvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesisCancer Sci9962702008 ChanSHYee KoJMChanKWChanYPTaoQHyytiainenMKeski-OjaJLawSSrivastavaGTangJTsaoSWChenHStanbridgeEJLungMLThe ECM protein LTBP-2 is a suppressor of esophageal squamous cell carcinoma tumor formation but higher tumor expression associates with poor patient outcomeInt J Cancer1295655732011 SathyanarayanaUGMaruyamaRPadarASuzukiMBondarukJSagalowskyAMinnaJDFrenkelEPGrossmanHBCzerniakBGazdarAFMolecular detection of noninvasive and invasive bladder tumor tissues and exfoliated cells by aberrant promoter methylation of laminin-5 encoding genesCancer Res64142514302004 SenchenkoVNKrasnovGSDmitrievAAKudryavtsevaAVAnedchenkoEABragaEAProninaIVKondratievaTTIvanovSVZabarovskyERLermanMIDifferential expression of CHL1 gene during development of major human cancersPLoS One6e156122011 do Carmo AvidesMGloverDMAbnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centersScience283173317351999 CheesemanIMHoriTFukagawaTDesaiAKNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebratesMol Biol Cell195875942008 HaywardDGFryAMNek2 kinase in chromosome instability and cancerCancer Lett2371551662006 NakanoIMasterman-SmithMSaigusaKPaucarAAHorvathSShoemakerLWatanabeMNegroABajpaiRHowesALelievreVWaschekJALazareffJAFreijeWALiauLMGilbertsonRJCloughesyTFGeschwindDHNelsonSFMischelPSTerskikhAVKornblumHIMaternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cellsJ Neurosci Res8648602008 JeongHRyuYJAnJLeeYKimAEpithelial-mesenchymal transition in breast cancer correlates with high histological grade and triple-negative phenotypeHistopathology60E87E952012 HorvathSZhangBCarlsonMLuKVZhuSFelcianoRMLauranceMFZhaoWQiSChenZLeeYScheckACLiauLMWuHGeschwindDHFebboPGKornblumHICloughesyTFNelsonSFMischelPSAnalysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular targetProc Natl Acad Sci USA10317402174072006 MoroiYPeeblesCFritzlerMJSteigerwaldJTanEMAutoantibody to centromere (kinetochore) in scleroderma seraProc Natl Acad Sci USA77162716311980 TomonagaTMatsushitaKYamaguchiSOohashiTShimadaHOchiaiTYodaKNomuraFOverexpression and mistargeting of centromere protein-A in human primary colorectal cancerCancer Res63351135162003 de la GuardiaCCasianoCATrinidad-PinedoJBáezACENP-F gene amplification and overexpression in head and neck squamous cell carcinomasHead Neck231041122001 GrützmannRPilarskyCAmmerpohlOLüttgesJBöhmeASiposBFoerderMAlldingerIJahnkeBSchackertHKKalthoffHKremerBKlöppelGSaegerHDGene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarraysNeoplasia66116222004 BiècheIVacherSLallemandFTozlu-KaraSBennaniHBeuzelinMDriouchKRouleauELereboursFRipocheHCizeron-ClairacGSpyratosFLidereauRExpression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidyMol Cancer10232011 HuZHuangGSadanandamAGuSLenburgMEPaiMBayaniNBlakelyEAGrayJWMaoJHThe expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancerBreast Cancer Res12R182010 Figures and Tables

Purification of TNBC cells or ductal epithelial cells from normal ducts by means of microdissection and TNBC gene expression profiling. (A) Representative images of purified cancer cells and normal ductal epithelial cells from TNBC. Pre-microdissected (left lane), post-microdissected (middle lane) and microdissected cells (right lane) are shown after hematoxylin and eosin staining. (B) Heat-map image representing 622 genes that were significantly upregulated or downregulated >5-fold in TNBC. (C) Heat-map showing upregulated genes compared with normal ductal cells with no expression in normal organs including the heart, lung, liver and kidney.

Gene annotation enrichment analysis based on DAVID was performed to elucidate the biological processes and pathways characterized in TNBC. Functional annotation terms are shown in bar plots; the value of the vertical axis represents the fold enrichment score of each term.

ASPM and CENPK expression profiles. (A) qRT-PCR results of ASPM and CENPK in microdissected tumor cells from 48 TNBC tissues and 13 normal ductal cells (Mann-Whitney t-test). (B) qRT-PCR results of ASPM and CENPK in five TNBC cell lines, MCF10A cells (human normal mammary epithelial cell line) and various normal organs (Student’s two-sided t-test: *P<0.05).

siRNA-mediated growth inhibitory effects in TNBC cells. (A) siRNA-mediated knockdown of ASPM in HCC1937 and BT-20 cells, and CENPK in HCC1937 and MDA-MB-231 cells was validated by qRT-PCR analysis (Student’s two-sided t-test: *P<0.05, **P<0.01). (B) The MTT assay showing a decrease in the number of cells upon ASPM knockdown in HCC1937 and BT-20 cells and CENPK knockdown in HCC1937 and MDA-MB-231 cells (Student’s two-sided t-test: *P<0.05, **P<0.01). (C) Colony formation assay (left) demonstrating a decrease in the number of colonies upon ASPM and CENPK knockdown (right) (Student’s two-sided t-test: *P<0.05).

Alteration of the cell cycle and changes in cancer cell morphology upon ASPM and CENPK knockdown in TNBC cells. (A) FACS analysis at each time-point. The proportion of cells at the G2/M phase was elevated 2 days after siASPM transfection followed by sub-G1 induction at 6 days in HCC1937 cells. (B) Upon CENPK knockdown, the proportion of cells at the G0/G1 phase was elevated in MDA-MB-231 cells at 2 days after siCENPK transfection, followed by sub-G1 induction at 6 days after transfection. A total of 10,000 cells were counted (Student’s two-sided t-test: *P<0.05, **P<0.01). (C) Immunocytochemical staining analysis of α/β-tubulin at 48 h after siRNA transfection. Enlarged siASPM-treated HCC1937 cells (arrowhead). Control cells that entered metaphase are indicated by the arrow. (D) Disruption of the structural integrity of tubulin in siCENPK-treated MDA-MB-231 cells (arrowhead). α/β-tubulin and nuclei staining are shown as green and blue, respectively. Scale bars, 50 μm.

Clinicopathological features of 48 TNBC patients.

ID Age Histology TNM Stage ER/PgR/HER2 Microarray RT-PCR
1 44 Papillo-tubular T0N3M1 IV −/−/0 Done Done
8 79 DCIS T1N0M0 I −/−/0 Not done Done
10 57 Papillo-tubular T1N0M0 I −/−/1+ Not done Done
19 63 Solid-tubular T1N0M0 I −/−/0 Not done Done
27 60 Solid-tubular T2N1M0 II −/−/0 Done Done
42 59 Solid-tubular T2N0M0 II −/−/0 Not done Done
44 79 Papillo-tubular Recurrence - −/−/1+ Not done Done
53 55 Papillo-tubular T1N0M0 I −/−/0 Not done Done
54 77 Solid-tubular T1N1M0 II −/−/0 Not done Done
56 28 Scirrhous T2N1M0 II −/−/0 Done Done
57 58 Solid-tubular T1N1M0 II −/−/0 Not done Done
60 54 Solid-tubular T2N1M0 II −/−/0 Done Done
64 60 Papillo-tubular T2N0M0 II −/−/0 Not done Done
66 59 Special type T2N1M0 II −/−/0 Not done Done
78 45 Solid-tubular T2N1M0 II −/−/0 Done Done
89 44 Papillo-tubular Recurrence - −/−/0 Not done Done
95 60 Solid-tubular T1N0M0 I −/−/0 Not done Done
101 60 Scirrhous T2N1M0 II −/−/0 Not done Done
110 77 Scirrhous T2N1M0 II −/−/1+ Not done Done
116 70 Solid-tubular T2N1M0 II −/−/0 Done Done
155 36 Solid-tubular T1N1M0 II −/−/0 Done Done
225 49 Papillo-tubular T2N1M0 II −/−/1+ Not done Done
252 49 Solid-tubular T2N1M0 II −/−/1+ Done Done
253 49 Scirrhous T2N1M0 II −/−/0 Done Done
265 80 Scirrhous T1N1M0 II −/−/0-1+ Done Done
313 53 Scirrhous T3N2M0 III −/−/0 Done Done
337 42 Solid-tubular T2N1M0 II −/−/1+ Done Done
359 55 Papillo-tubular T2N0M0 II −/−/0 Done Done
362 37 Papillo-tubular T2N1M0 II −/−/0 Done Done
363 69 Papillo-tubular T2N0M0 II −/−/0 Done Done
366 61 Special type T2N1M0 II −/−/0-1+ Done Done
384 32 Papillo-tubular T3N0M0 II −/−/0 Done Done
392 46 Papillo-tubular T1N1M0 II −/−/0 Done Done
414 60 Papillo-tubular T2N1M0 II −/−/1+ Not done Done
415 54 Solid-tubular T2N0M0 II −/−/1+ Done Done
420 41 Solid-tubular T3N0M0 II −/−/0 Done Done
423 70 Solid-tubular T2N0M0 II −/−/0 Done Done
438 63 Solid-tubular T3N0M0 II −/−/0 Done Done
445 39 Solid-tubular T2N1M0 II −/−/0 Done Done
453 50 Solid-tubular T2N1M0 II −/−/0 Done Done
481 59 Solid-tubular T3N1M0 III −/−/0 Done Done
528 55 Solid-tubular T2N1M0 II −/−/0 Done Done
535 58 Solid-tubular T2N1M0 II −/−/0 Not done Done
553 71 Solid-tubular T0N1M0 II −/−/1+ Not done Done
558 56 Solid-tubular T2N1M0 II −/−/0 Done Done
562 64 Scirrhous T2N0M0 II −/−/0 Done Done
566 52 Solid-tubular T3N1M0 III −/−/0 Done Done
651 45 Scirrhous T2N1M0 II −/−/0 Done Done

DCIS, ductal carcinoma in situ; papillo-tubular, papillo-tubular adenocarcinoma; solid-tubular, solid-tubular adenocarcinoma; scirrhous, scirrhous carcinoma; special type ID 66, adenocarcinoma with squamous cell carcinoma; ID 366, osseous metaplasia; case 44, axillary lymph node metastasis was diagnosed 8 months after the first surgery followed by the dissection of metastatic lymph nodes; case 89, local recurrence in residual breast occurred after 2 years of the first surgery followed by a lumpectomy. All information was judged according to the General Rules for Clinical and Pathological Recording of Breast Cancer (The Japanese Breast Cancer Society). T, tumor stage; N, lymph node metastasis status; M, distant metastasis.

Genes significantly upregulated in TNBC compared with normal ductal cells.

Probe ID Accession no. Symbol Gene name Fold change (log) P-value
A_24_P334130 NM_054034 FN1 Fibronectin 1 5.33 1.26E-04
A_24_P940678 N/A N/A 5.07 1.26E-04
A_23_P367618 NM_003412 ZIC1 Zic family member 1 (odd-paired homolog, Drosophila) 5.01 1.26E-04
A_23_P118834 NM_001067 TOP2A Topoisomerase (DNA) IIα 170 kDa 4.76 1.26E-04
A_32_P119154 BE138567 N/A 4.75 1.26E-04
A_23_P35219 NM_002497 NEK2 NIMA (never in mitosis gene a)-related kinase 2 4.67 1.26E-04
A_23_P166360 NM_206956 PRAME Preferentially expressed antigen in melanoma 4.64 1.26E-04
A_24_P332314 NM_198947 FAM111B Family with sequence similarity 111, member B 4.63 1.26E-04
A_24_P413884 NM_001809 CENPA Centromere protein A 4.59 1.26E-04
A_23_P68610 NM_012112 TPX2 TPX2, microtubule-associated, homolog (Xenopus laevis) 4.58 1.26E-04
A_23_P58266 NM_005980 S100P S100 calcium binding protein P 4.57 1.26E-04
A_24_P297539 NM_181803 UBE2C Ubiquitin-conjugating enzyme E2C 4.49 1.26E-04
A_23_P401 NM_016343 CENPF Centromere protein F, 350/400 ka (mitosin) 4.44 1.26E-04
A_23_P57379 NM_003504 CDC45L CDC45 cell division cycle 45-like (S. cerevisiae) 4.44 1.26E-04
A_23_P118815 NM_001012271 BIRC5 Baculoviral IAP repeat-containing 5 4.43 1.26E-04
A_23_P210853 NM_021067 GINS1 GINS complex subunit 1 (Psf1 homolog) 4.41 1.26E-04
A_23_P258493 NM_005573 LMNB1 Lamin B1 4.31 1.26E-04
A_24_P119745 NM_212482 FN1 Fibronectin 1 4.31 1.26E-04
A_24_P680947 BC044933 KIF18B Kinesin family member 18B 4.3 1.26E-04
A_32_P92642 N/A N/A 4.3 1.26E-04
A_23_P356684 NM_018685 ANLN Anillin, actin binding protein 4.29 1.26E-04
A_24_P314571 BU616832 N/A 4.24 1.26E-04
A_23_P98580 NM_004265 FADS2 Fatty acid desaturase 2 4.2 1.26E-04
A_23_P52017 NM_018136 ASPM asp (abnormal spindle) homolog, microcephaly associated (Drosophila) 4.17 1.26E-04
A_24_P20607 NM_005409 CXCL11 Chemokine (C-X-C motif) ligand 11 4.16 2.33E-04
A_32_P199884 NM_032132 HORMAD1 HORMA domain containing 1 4.13 2.33E-04
A_23_P70007 NM_012484 HMMR Hyaluronan-mediated motility receptor (RHAMM) 4.11 1.26E-04
A_23_P22378 NM_003108 SOX11 SRY (sex determining region Y)-box 11 4.1 1.26E-04
A_23_P259586 NM_003318 TTK TTK protein kinase 4.09 1.26E-04
A_23_P200310 NM_017779 DEPDC1 DEP domain containing 1 4.08 1.26E-04
A_24_P378331 NM_170589 CASC5 Cancer susceptibility candidate 5 4.06 1.26E-04
A_23_P111888 NM_138455 CTHRC1 Collagen triple helix repeat containing 1 4.05 1.26E-04
A_23_P48835 NM_138555 KIF23 Kinesin family member 23 4.05 1.26E-04
A_23_P115872 NM_018131 CEP55 Centrosomal protein 55 kDa 4.03 1.26E-04
A_23_P132956 NM_004181 UCHL1 Ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) 4.03 1.26E-04
A_24_P911179 NM_018136 ASPM asp (abnormal spindle) homolog, microcephaly associated (Drosophila) 4.02 1.26E-04
A_23_P408955 NM_004091 E2F2 E2F transcription factor 2 4.02 1.26E-04
A_23_P7636 NM_004219 PTTG1 Pituitary tumor-transforming 1 4 1.26E-04
A_23_P204941 NM_004004 GJB2 Gap junction protein, β2, 26 kDa 4 1.26E-04
A_23_P18452 NM_002416 CXCL9 Chemokine (C-X-C motif) ligand 9 3.94 2.33E-04
A_24_P96780 NM_016343 CENPF Centromere protein F, 350/400 ka (mitosin) 3.92 1.26E-04
A_23_P69537 NM_006681 NMU Neuromedin U 3.9 1.26E-04
A_24_P14156 NM_006101 NDC80 NDC80 homolog, kinetochore complex component (S. cerevisiae) 3.86 1.26E-04
A_23_P254733 NM_024629 MLF1IP MLF1 interacting protein 3.85 1.26E-04
A_23_P74115 NM_003579 RAD54L RAD54-like (S. cerevisiae) 3.84 1.26E-04
A_23_P50108 NM_006101 NDC80 NDC80 homolog, kinetochore complex component (S. cerevisiae) 3.84 1.26E-04
A_24_P150160 NM_004265 FADS2 Fatty acid desaturase 2 3.83 1.26E-04
A_23_P155815 NM_022346 NCAPG Non-SMC condensin I complex, subunit G 3.82 1.26E-04
A_23_P125278 NM_005409 CXCL11 Chemokine (C-X-C motif) ligand 11 3.81 1.26E-04
A_23_P51085 NM_020675 SPC25 SPC25, NDC80 kinetochore complex component, homolog (S. cerevisiae) 3.81 1.26E-04
A_23_P133123 NM_032117 MND1 Meiotic nuclear divisions 1 homolog (S. cerevisiae) 3.8 1.26E-04
A_32_P62997 NM_018492 PBK PDZ binding kinase 3.8 1.26E-04
A_23_P256956 NM_005733 KIF20A Kinesin family member 20A 3.79 1.26E-04
A_24_P933613 N/A N/A 3.78 1.26E-04
A_23_P212844 NM_006342 TACC3 Transforming, acidic coiled-coil containing protein 3 3.78 1.26E-04
A_24_P254705 NM_020394 ZNF695 Zinc finger protein 695 3.76 1.26E-04
A_23_P115482 NM_014176 UBE2T Ubiquitin-conjugating enzyme E2T (putative) 3.75 1.26E-04
A_32_P201723 N/A N/A 3.73 1.26E-04
A_23_P256425 NM_014479 ADAMDEC1 ADAM-like, decysin 1 3.73 1.26E-04
A_23_P432352 NM_001017978 CXorf61 Chromosome X open reading frame 61 3.73 1.26E-04
A_23_P208880 NM_013282 UHRF1 Ubiquitin-like with PHD and ring finger domains 1 3.72 1.26E-04
A_23_P323751 NM_030919 FAM83D Family with sequence similarity 83, member D 3.71 1.26E-04
A_23_P48669 NM_005192 CDKN3 Cyclin-dependent kinase inhibitor 3 3.71 1.26E-04
A_24_P234196 NM_001034 RRM2 Ribonucleotide reductase M2 3.69 1.26E-04
A_23_P253791 NM_004345 CAMP Cathelicidin antimicrobial peptide 3.69 1.26E-04
A_23_P76914 NM_005982 SIX1 SIX homeobox 1 3.67 4.43E-04
A_23_P94571 NM_004432 ELAVL2 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 2 (Hu antigen B) 3.67 1.26E-04
A_23_P200222 NM_033300 LRP8 Low density lipoprotein receptor-related protein 8, apolipoprotein E receptor 3.67 1.26E-04
A_24_P416079 NM_016359 NUSAP1 Nucleolar and spindle associated protein 1 3.66 1.26E-04
A_23_P104651 NM_080668 CDCA5 Cell division cycle associated 5 3.65 1.26E-04
A_23_P150667 NM_031217 KIF18A Kinesin family member 18A 3.64 1.26E-04
A_24_P859859 N/A N/A 3.63 4.43E-04
A_23_P312150 NM_001956 EDN2 Endothelin 2 3.61 1.26E-04
A_23_P375 NM_018101 CDCA8 Cell division cycle associated 8 3.59 1.26E-04
A_32_P68525 BC035392 N/A 3.58 1.26E-04
A_23_P43490 NM_058197 CDKN2A Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 3.56 1.26E-04
A_23_P1691 NM_002421 MMP1 Matrix metallopeptidase 1 (interstitial collagenase) 3.55 1.26E-04
A_23_P117852 NM_014736 KIAA0101 KIAA0101 3.54 1.26E-04
A_24_P319613 NM_002497 NEK2 NIMA (never in mitosis gene a)-related kinase 2 3.53 1.26E-04
A_23_P10385 NM_016448 DTL Denticleless homolog (Drosophila) 3.53 1.26E-04
A_32_P1173 NM_138441 C6orf150 Chromosome 6 open reading frame 150 3.51 1.26E-04
A_23_P94422 NM_014791 MELK Maternal embryonic leucine zipper kinase 3.5 1.26E-04
A_23_P340909 BC013418 SKA3 Spindle and kinetochore associated complex subunit 3 3.48 1.26E-04
A_23_P385861 NM_152562 CDCA2 Cell division cycle associated 2 3.47 1.26E-04
A_23_P124417 NM_004336 BUB1 Budding uninhibited by benzimidazoles 1 homolog (yeast) 3.47 1.26E-04
A_24_P257099 NM_018410 HJURP Holliday junction recognition protein 3.43 1.26E-04
A_24_P270460 NM_005532 IFI27 Interferon, α-inducible protein 27 3.41 2.33E-04
A_23_P206059 NM_003981 PRC1 Protein regulator of cytokinesis 1 3.39 1.26E-04
A_23_P74349 NM_145697 NUF2 NUF2, NDC80 kinetochore complex component, homolog (S. cerevisiae) 3.36 1.26E-04
A_24_P302584 NM_003108 SOX11 SRY (sex determining region Y)-box 11 3.36 4.43E-04
A_24_P68088 NR_002947 TCAM1 Testicular cell adhesion molecule 1 homolog (mouse) 3.35 2.33E-04
A_24_P605612 NM_003247 THBS2 Thrombospondin 2 3.34 1.26E-04
A_24_P366033 NM_018098 ECT2 Epithelial cell transforming sequence 2 oncogene 3.34 1.26E-04
A_23_P93258 NM_003537 HIST1H3B Histone cluster 1, H3b 3.33 1.26E-04
A_23_P211762 N/A COL8A1 Collagen, type VIII, α1 3.29 4.43E-04
A_23_P77493 NM_006086 TUBB3 Tubulin, β3 3.29 1.26E-04
A_23_P204947 NM_004004 GJB2 Gap junction protein, β2, 26 kDa 3.29 1.26E-04
A_23_P149668 NM_014875 KIF14 Kinesin family member 14 3.29 1.26E-04
A_23_P34325 NM_033300 LRP8 Low density lipoprotein receptor-related protein 8, apolipoprotein E receptor 3.28 1.26E-04
A_32_P56154 N/A N/A 3.28 1.26E-04
A_32_P10403 BU618641 SERPINE1 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 3.27 1.26E-04
A_23_P138507 NM_001786 CDC2 Cell division cycle 2, G1→S and G2→M 3.24 1.26E-04
A_23_P48513 NM_005532 IFI27 Interferon, α-inducible protein 27 3.23 1.26E-04
A_23_P49972 NM_001254 CDC6 Cell division cycle 6 homolog (S. cerevisiae) 3.22 1.26E-04
A_24_P306896 XR_040656 LOC283711 Hypothetical protein LOC283711 3.22 1.26E-04
A_23_P44684 NM_018098 ECT2 Epithelial cell transforming sequence 2 oncogene 3.21 1.26E-04
A_24_P161773 N/A N/A 3.2 1.26E-04
A_23_P100344 NM_014321 ORC6L Origin recognition complex, subunit 6 like (yeast) 3.2 1.26E-04
A_32_P162183 NM_000063 C2 Complement component 2 3.18 1.26E-04
A_23_P163481 NM_001211 BUB1B Budding uninhibited by benzimidazoles 1 homolog β (yeast) 3.17 1.26E-04
A_32_P113784 N/A N/A 3.16 1.26E-04
A_32_P87849 N/A N/A 3.16 1.26E-04
A_24_P397107 NM_001789 CDC25A Cell division cycle 25 homolog A (S. pombe) 3.15 1.26E-04
A_23_P209200 NM_001238 CCNE1 Cyclin E1 3.15 1.26E-04
A_32_P16625 N/A N/A 3.15 1.26E-04
A_23_P58321 NM_001237 CCNA2 Cyclin A2 3.15 1.26E-04
A_24_P37903 N/A LOX Lysyl oxidase 3.12 1.26E-04
A_32_P64919 NM_001042517 DIAPH3 Diaphanous homolog 3 (Drosophila) 3.12 1.26E-04
A_23_P379614 NM_007280 OIP5 Opa interacting protein 5 3.12 1.26E-04
A_23_P206441 NM_000135 FANCA Fanconi anemia, complementation group A 3.09 1.26E-04
A_23_P16915 NM_012413 QPCT Glutaminyl-peptide cyclotransferase 3.09 1.26E-04
A_23_P137173 NM_021992 TMSB15A Thymosin β 15a 3.07 1.26E-04
A_24_P313504 NM_005030 PLK1 Polo-like kinase 1 (Drosophila) 3.07 1.26E-04
A_23_P251421 NM_031942 CDCA7 Cell division cycle associated 7 3.06 1.26E-04
A_23_P252292 NM_006733 CENPI Centromere protein I 3.04 1.26E-04
A_23_P158725 NM_001042422 SLC16A3 Solute carrier family 16, member 3 (monocarboxylic acid transporter 4) 3.04 1.26E-04
A_23_P57417 NM_005940 MMP11 Matrix metallopeptidase11 (stromelysin 3) 3.03 1.26E-04
A_24_P291044 N/A N/A 3.02 1.26E-04
A_23_P343927 NM_175065 HIST2H2AB Histone cluster 2, H2ab 3.01 1.26E-04
A_23_P63789 NM_032997 ZWINT ZW10 interactor 3.01 1.26E-04
A_23_P123596 NM_000170 GLDC Glycine dehydrogenase (decarboxylating) 3 1.26E-04
A_23_P88731 NM_002875 RAD51 RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) 3 1.26E-04
A_23_P161474 NM_182751 MCM10 Minichromosome maintenance complex component 10 2.99 1.26E-04
A_24_P303354 NM_021064 HIST1H2AG Histone cluster 1, H2ag 2.98 1.26E-04
A_23_P10518 NM_016521 TFDP3 Transcription factor Dp family, member 3 2.98 1.26E-04
A_24_P247660 NM_001002033 HN1 Hematological and neurological expressed 1 2.97 1.26E-04
A_23_P134910 NM_003878 GGH γ-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase) 2.97 1.26E-04
A_32_P7193 N/A N/A 2.97 1.26E-04
A_23_P49878 NM_019013 FAM64A Family with sequence similarity 64, member A 2.96 1.26E-04
A_24_P359231 BC014312 HIST1H2BJ Histone cluster 1, H2bj 2.95 1.26E-04
A_32_P140262 N/A N/A 2.95 1.26E-04
A_23_P55270 NM_002988 CCL18 Chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated) 2.95 1.26E-04
A_24_P462899 NM_001012507 C6orf173 Chromosome 6 open reading frame 173 2.94 1.26E-04
A_23_P502520 NM_172374 IL4I1 Interleukin 4 induced 1 2.94 1.26E-04
A_23_P253762 N/A N/A 2.94 1.26E-04
A_23_P214908 AY374131 N/A 2.94 1.26E-04
A_24_P225534 NM_017821 RHBDL2 Rhomboid, veinlet-like 2 (Drosophila) 2.94 1.26E-04
A_23_P203419 NM_013402 FADS1 Fatty acid desaturase 1 2.94 1.26E-04
A_23_P150935 NM_005480 TROAP Trophinin associated protein (tastin) 2.94 1.26E-04
A_24_P412088 NM_182751 MCM10 Minichromosome maintenance complex component 10 2.94 1.26E-04
A_23_P71727 NM_001827 CKS2 CDC28 protein kinase regulatory subunit 2 2.93 1.26E-04
A_23_P217236 NM_005342 HMGB3 High-mobility group box 3 2.92 1.26E-04
A_32_P109296 NM_152259 C15orf42 Chromosome 15 open reading frame 42 2.91 1.26E-04
A_23_P89509 NM_006461 SPAG5 Sperm associated antigen 5 2.91 1.26E-04
A_24_P563068 N/A N/A 2.91 1.26E-04
A_23_P416468 NM_025049 PIF1 PIF1 5′-to-3′ DNA helicase homolog (S. cerevisiae) 2.91 1.26E-04
A_24_P38895 NM_002105 H2AFX H2A histone family, member X 2.9 1.26E-04
A_23_P52278 NM_004523 KIF11 Kinesin family member 11 2.89 1.26E-04
A_24_P144543 N/A N/A 2.89 1.26E-04
A_24_P71468 NM_012413 QPCT Glutaminyl-peptide cyclotransferase 2.88 2.33E-04
A_23_P116123 NM_001274 CHEK1 CHK1 checkpoint homolog (S. pombe) 2.88 1.26E-04
A_32_P106235 N/A N/A 2.87 1.26E-04
A_24_P139152 AL359062 COL8A1 Collagen, type VIII, α1 2.87 4.43E-04
A_23_P36831 NM_003979 GPRC5A G protein-coupled receptor, family C, group 5, member A 2.87 1.26E-04
A_23_P387471 NM_005931 MICB MHC class I polypeptide-related sequence B 2.85 1.26E-04
A_23_P9574 NM_018098 ECT2 Epithelial cell transforming sequence 2 oncogene 2.84 1.26E-04
A_24_P535256 AK001903 INHBA Inhibin, βA 2.84 1.26E-04
A_24_P76521 AK056691 GSG2 germ cell associated 2 (haspin) 2.83 1.26E-04
A_23_P103795 NM_138959 VANGL1 vang-like 1 (van gogh, Drosophila) 2.83 1.26E-04
A_32_P74409 NM_001145033 LOC387763 Hypothetical protein LOC387763 2.83 1.26E-04
A_23_P100632 NM_001002033 HN1 Hematological and neurological expressed 1 2.83 1.26E-04
A_23_P126212 NM_022111 CLSPN Claspin homolog (Xenopus laevis) 2.83 1.26E-04
A_24_P659113 NM_152523 CCNYL1 Cyclin Y-like 1 2.83 1.26E-04
A_24_P367227 NM_001144755 MYBL1 v-myb myeloblastosis viral oncogene homolog (avian)-like 1 2.82 1.26E-04
A_23_P162719 NM_030932 DIAPH3 Diaphanous homolog 3 (Drosophila) 2.81 1.26E-04
A_32_P221799 NM_003514 HIST1H2AM Histone cluster 1, H2am 2.81 1.26E-04
A_23_P60120 NM_031415 GSDMC Gasdermin C 2.81 2.33E-04
A_24_P902509 NM_018193 FANCI Fanconi anemia, complementation group I 2.8 1.26E-04
A_23_P50096 NM_001071 TYMS Thymidylate synthetase 2.79 1.26E-04
A_32_P143245 NM_001012507 C6orf173 Chromosome 6 open reading frame 173 2.79 1.26E-04
A_23_P155969 NM_014264 PLK4 Polo-like kinase 4 (Drosophila) 2.79 1.26E-04
A_23_P62021 N/A N/A 2.78 1.26E-04
A_32_P183218 NM_153695 ZNF367 Zinc finger protein 367 2.77 1.26E-04
A_23_P46118 NM_001821 CHML Choroideremia-like (Rab escort protein 2) 2.76 2.33E-04
A_23_P327643 N/A N/A 2.75 1.26E-04
A_23_P375104 NM_018193 FANCI Fanconi anemia, complementation group I 2.75 1.26E-04
A_23_P1823 NM_000280 PAX6 Paired box 6 2.75 1.26E-04
A_23_P168014 NM_021066 HIST1H2AJ Histone cluster 1, H2aj 2.74 1.26E-04
A_24_P413126 NM_020182 PMEPA1 Prostate transmembrane protein, androgen induced 1 2.74 1.26E-04
A_23_P80032 NM_005225 E2F1 E2F transcription factor 1 2.74 1.26E-04
A_23_P215976 NM_057749 CCNE2 Cyclin E2 2.72 2.33E-04
A_32_P231415 AF132203 SCD Stearoyl-CoA desaturase (δ-9-desaturase) 2.72 1.26E-04
A_23_P370989 NM_005914 MCM4 Minichromosome maintenance complex component 4 2.72 1.26E-04
A_23_P216429 NM_017680 ASPN Asporin 2.71 1.26E-04
A_24_P195621 NR_027288 LOC341056 SUMO-1 activating enzyme subunit 1 pseudogene 2.71 1.26E-04
A_32_P151800 NM_207418 FAM72D Family with sequence similarity 72, member D 2.7 1.26E-04
A_23_P122197 NM_031966 CCNB1 Cyclin B1 2.7 1.26E-04
A_23_P34788 NM_006845 KIF2C Kinesin family member 2C 2.7 1.26E-04
A_32_P206698 NM_001826 CKS1B CDC28 protein kinase regulatory subunit 1B 2.7 1.26E-04
A_23_P99292 NM_006479 RAD51AP1 RAD51 associated protein 1 2.7 1.26E-04
A_23_P133956 NM_002263 KIFC1 Kinesin family member C1 2.69 1.26E-04
A_32_P143496 N/A N/A 2.69 1.26E-04
A_32_P163858 NM_005063 SCD Stearoyl-CoA desaturase (δ-9-desaturase) 2.69 1.26E-04
A_32_P175557 R01145 N/A 2.69 1.26E-04
A_23_P63618 NM_005063 SCD Stearoyl-CoA desaturase (δ-9-desaturase) 2.69 1.26E-04
A_23_P88630 NM_000057 BLM Bloom syndrome, RecQ helicase-like 2.68 1.26E-04
A_24_P276102 NM_183404 RBL1 Retinoblastoma-like 1 (p107) 2.68 1.26E-04
A_23_P135385 N/A N/A 2.68 1.26E-04
A_23_P57658 NM_020386 HRASLS HRAS-like suppressor 2.67 1.26E-04
A_23_P23303 NM_003686 EXO1 Exonuclease 1 2.67 1.26E-04
A_23_P88691 NM_000745 CHRNA5 Cholinergic receptor, nicotinic, α5 2.67 1.26E-04
A_24_P923381 NR_002219 EPR1 Effector cell peptidase receptor 1 (non-protein coding) 2.66 1.26E-04
A_23_P24444 NM_001360 DHCR7 7-dehydrocholesterol reductase 2.65 1.26E-04
A_23_P43157 NM_001080416 MYBL1 v-myb myeloblastosis viral oncogene homolog (avian)-like 1 2.65 2.33E-04
A_23_P88740 NM_018455 CENPN Centromere protein N 2.64 1.26E-04
A_23_P131866 NM_198433 AURKA Aurora kinase A 2.64 1.26E-04
A_23_P259641 NM_004456 EZH2 Enhancer of zeste homolog 2 (Drosophila) 2.64 1.26E-04
A_32_P72341 NM_173084 TRIM59 Tripartite motif-containing 59 2.62 1.26E-04
A_24_P227091 NM_004523 KIF11 Kinesin family member 11 2.61 1.26E-04
A_23_P145238 NM_080593 HIST1H2BK Histone cluster 1, H2bk 2.61 1.26E-04
A_23_P136805 NM_014783 ARHGAP11A Rho GTPase activating protein 11A 2.6 1.26E-04
A_23_P167997 NM_003518 HIST1H2BG Histone cluster 1, H2bg 2.6 1.26E-04
A_23_P63402 NM_013296 GPSM2 G-protein signaling modulator 2 (AGS3-like, C. elegans) 2.6 1.26E-04
A_24_P192994 NM_013402 FADS1 Fatty acid desaturase 1 2.59 1.26E-04
A_23_P25559 NM_005845 ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 2.59 3.41E-04
A_23_P309381 NM_001040874 HIST2H2AA4 Histone cluster 2, H2aa4 2.59 1.26E-04
A_23_P35871 NM_024680 E2F8 E2F transcription factor 8 2.58 1.26E-04
A_23_P207307 N/A N/A 2.58 1.26E-04
A_24_P399888 NM_001002876 CENPM Centromere protein M 2.58 1.26E-04
A_23_P360754 NM_005099 ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif, 4 2.57 3.41E-04
A_23_P21706 NM_001905 CTPS CTP synthase 2.57 1.26E-04
A_24_P174924 NM_003537 HIST1H3B Histone cluster 1, H3b 2.57 1.26E-04
A_23_P155989 NM_022145 CENPK Centromere protein K 2.57 1.26E-04
A_23_P103981 NM_001040874 HIST2H2AA4 Histone cluster 2, H2aa4 2.56 1.26E-04
A_23_P571 NM_006516 SLC2A1 Solute carrier family 2 (facilitated glucose transporter), member 1 2.56 1.26E-04
A_23_P420551 NM_007174 CIT Citron (rho-interacting, serine/threonine kinase 21) 2.56 1.26E-04
A_23_P411335 NM_152524 SGOL2 Shugoshin-like 2 (S. pombe) 2.54 1.26E-04
A_32_P147090 NM_199357 ARHGAP11A Rho GTPase activating protein 11A 2.54 1.26E-04
A_23_P70448 NM_005325 HIST1H1A Hstone cluster 1, H1a 2.53 1.26E-04
A_23_P43484 NM_058197 CDKN2A Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 2.52 1.26E-04
A_24_P85539 NM_212482 FN1 Fibronectin 1 2.52 1.26E-04
A_32_P28704 N/A N/A 2.52 1.26E-04
A_23_P107421 NM_003258 TK1 Thymidine kinase 1, soluble 2.51 1.26E-04
A_23_P502425 NM_020409 MRPL47 Mitochondrial ribosomal protein L47 2.5 1.26E-04
A_24_P351466 NM_020890 KIAA1524 KIAA1524 2.5 1.26E-04
A_23_P211910 NM_182943 PLOD2 Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 2.5 1.26E-04
A_24_P9321 NM_003533 HIST1H3I Histone cluster 1, H3i 2.49 1.26E-04
A_24_P334248 NM_014996 PLCH1 Phospholipase C, eta 1 2.48 1.26E-04
A_24_P819890 NM_001005210 LRRC55 Leucine rich repeat containing 55 2.48 4.43E-04
A_23_P146456 NM_001333 CTSL2 Cathepsin L2 2.48 2.33E-04
A_24_P242440 NM_003780 B4GALT2 UDP-Gal:βGlcNAc β 1,4-galactosyltransferase, polypeptide 2 2.47 1.26E-04
A_23_P88331 NM_014750 DLGAP5 Discs, large (Drosophila) homolog-associated protein 5 2.47 1.26E-04
A_23_P216068 NM_014109 ATAD2 ATPase family, AAA domain containing 2 2.46 1.26E-04
A_32_P31021 N/A N/A 2.46 1.26E-04
A_23_P373119 NR_002165 HMGB3L1 High-mobility group box 3-like 1 2.46 1.26E-04
A_23_P361419 NM_018369 DEPDC1B DEP domain containing 1B 2.45 1.26E-04
A_23_P10870 NM_014908 DOLK Dolichol kinase 2.44 1.26E-04
A_23_P420692 NM_015053 PPFIA4 Protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), α4 2.43 1.26E-04
A_23_P146284 NM_003129 SQLE Squalene epoxidase 2.43 1.26E-04
A_32_P159254 AK123584 N/A 2.43 2.33E-04
A_23_P25626 NM_024808 C13orf34 Chromosome 13 open reading frame 34 2.43 1.26E-04
A_23_P59005 NM_000593 TAP1 Transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 2.43 2.33E-04
A_24_P49747 XM_929965 LOC646993 Similar to high mobility group box 3 2.43 1.26E-04
A_23_P252740 NM_024094 DSCC1 Defective in sister chromatid cohesion 1 homolog (S. cerevisiae) 2.42 1.26E-04
A_23_P397341 NM_152341 PAQR4 Progestin and adipoQ receptor family member IV 2.42 1.26E-04
A_23_P59045 NM_021052 HIST1H2AE Histone cluster 1, H2ae 2.42 1.26E-04
A_23_P140316 NM_001099652 GPR137C G protein-coupled receptor 137C 2.42 1.26E-04
A_23_P207520 Z74615 COL1A1 Collagen, type I, α1 2.41 1.26E-04
A_24_P920968 NM_182625 GEN1 Gen homolog 1, endonuclease (Drosophila) 2.41 1.26E-04
A_23_P366216 NM_003524 HIST1H2BH Histone cluster 1, H2bh 2.41 1.26E-04
A_23_P217049 NM_014286 FREQ Frequenin homolog (Drosophila) 2.41 2.33E-04
A_32_P194264 NM_001008708 CHAC2 ChaC, cation transport regulator homolog 2 (E. coli) 2.4 2.33E-04
A_32_P35839 N/A N/A 2.4 1.26E-04
A_23_P154894 NM_000100 CSTB Cystatin B (stefin B) 2.4 1.26E-04
A_24_P340066 NM_001421 ELF4 E74-like factor 4 (ets domain transcription factor) 2.4 1.26E-04
A_24_P857404 NM_001093725 MEX3A mex-3 homolog A (C. elegans) 2.4 1.26E-04
A_24_P133488 NM_017955 CDCA4 Cell division cycle associated 4 2.4 1.26E-04
A_23_P339240 NM_014996 PLCH1 Phospholipase C, eta 1 2.39 2.33E-04
A_23_P52410 NM_145307 RTKN2 Rhotekin 2 2.39 1.26E-04
A_23_P59877 NM_001444 FABP5 Fatty acid binding protein 5 (psoriasis-associated) 2.39 1.26E-04
A_23_P29594 NM_052969 RPL39L Ribosomal protein L39-like 2.38 1.26E-04
A_23_P11984 NM_201649 SLC6A9 Solute carrier family 6 (neurotransmitter transporter, glycine), member 9 2.38 2.33E-04
A_23_P200866 NM_203401 STMN1 Stathmin 1 2.37 1.26E-04
A_32_P182135 N/A N/A 2.36 1.26E-04
A_24_P323598 NM_001017420 ESCO2 Establishment of cohesion 1 homolog 2 (S. cerevisiae) 2.36 1.26E-04
A_23_P39574 NM_001080539 CCDC150 Coiled-coil domain containing 150 2.36 1.26E-04
A_24_P275386 AK025766 BRI3BP BRI3 binding protein 2.36 1.26E-04
A_23_P85460 NM_078626 CDKN2C Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) 2.35 1.26E-04
A_23_P57306 NM_005441 CHAF1B Chromatin assembly factor 1, subunit B (p60) 2.35 1.26E-04
A_23_P335329 NM_004485 GNG4 Guanine nucleotide binding protein (G protein), γ4 2.35 2.33E-04
A_23_P92441 NM_002358 MAD2L1 MAD2 mitotic arrest deficient-like 1 (yeast) 2.35 1.26E-04
A_24_P13390 NM_032814 RNFT2 Ring finger protein, transmembrane 2 2.35 1.26E-04
A_23_P362046 NM_138779 C13orf27 Chromosome 13 open reading frame 27 2.34 1.26E-04
A_23_P24716 NM_017870 TMEM132A Transmembrane protein 132A 2.34 1.26E-04
A_23_P91900 NM_005496 SMC4 structural maintenance of chromosomes 4 2.33 1.26E-04
A_24_P105102 NM_182687 PKMYT1 Protein kinase, membrane associated tyrosine/threonine 1 2.33 1.26E-04
A_24_P244420 NM_018367 ACER3 alkaline ceramidase 3 2.33 2.33E-04
A_23_P112673 NM_017975 ZWILCH Zwilch, kinetochore associated, homolog (Drosophila) 2.33 1.26E-04
A_23_P87769 NM_017915 C12orf48 Chromosome 12 open reading frame 48 2.33 1.26E-04
A_24_P296254 NM_014783 ARHGAP11A Rho GTPase activating protein 11A 2.32 1.26E-04
A_23_P166306 NM_000071 CBS Cystathionine-β-synthase 2.32 1.26E-04

N/A, not annotated; P-value, Benjamini-Hochberg false discovery rate of random permutation test; log fold change, between groups.Gene symbol, accession number and gene name were exported from GeneSpring (from the NCBI databases).

Significantly downregulated genes in TNBC compared with normal ductal cells.

Probe ID Accession no. Symbol Gene name Fold change (log) P-value
A_23_P127781 NM_006552 SCGB1D1 Secretoglobin, family 1D, member 1 −6.77 1.26E-04
A_32_P234405 CK570316 N/A −6.62 1.26E-04
A_23_P150555 NM_006551 SCGB1D2 Secretoglobin, family 1D, member 2 −6.51 1.26E-04
A_23_P12533 NM_052997 ANKRD30A Ankyrin repeat domain 30A −6.44 1.26E-04
A_23_P8702 NM_002652 PIP Prolactin-induced protein −6.34 1.26E-04
A_23_P501010 NM_000494 COL17A1 Collagen, type XVII, α1 −5.69 1.26E-04
A_24_P844984 NM_002644 PIGR Polymeric immunoglobulin receptor −5.55 1.26E-04
A_32_P216520 NM_007191 WIF1 WNT inhibitory factor 1 −5.53 1.26E-04
A_23_P71364 NM_015886 PI15 Peptidase inhibitor 15 −5.33 1.26E-04
A_24_P273756 NM_003722 TP63 Tumor protein p63 −5.11 1.26E-04
A_23_P132619 NM_000916 OXTR Oxytocin receptor −4.89 1.26E-04
A_32_P111873 BQ432543 N/A −4.88 1.26E-04
A_32_P23272 N/A N/A −4.85 1.26E-04
A_24_P643776 N/A N/A −4.74 1.26E-04
A_23_P136777 NM_001647 APOD Apolipoprotein D −4.71 1.26E-04
A_23_P9711 NM_006040 HS3ST4 Heparan sulfate (glucosamine) 3-O-sulfotransferase 4 −4.58 1.26E-04
A_23_P305292 NR_027180 LOC728264 Hypothetical LOC728264 −4.57 1.26E-04
A_23_P159974 NM_033495 KLHL13 Kelch-like 13 (Drosophila) −4.55 1.26E-04
A_23_P105144 NM_020974 SCUBE2 Signal peptide, CUB domain, EGF-like 2 −4.51 1.26E-04
A_32_P14253 N/A N/A −4.47 1.26E-04
A_23_P327380 NM_003722 TP63 Tumor protein p63 −4.45 1.26E-04
A_23_P337270 AK057247 N/A −4.43 1.26E-04
A_23_P420442 NM_153618 SEMA6D Sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D −4.34 1.26E-04
A_23_P8812 N/A N/A −4.3 1.26E-04
A_23_P160377 NM_003462 DNALI1 Dynein, axonemal, light intermediate chain 1 −4.26 1.26E-04
A_24_P92680 AK093340 LOC100132116 Hypothetical LOC100132116 −4.23 1.26E-04
A_23_P216779 NM_001007097 NTRK2 Neurotrophic tyrosine kinase, receptor, type 2 −4.23 1.26E-04
A_23_P148249 NM_024817 THSD4 Thrombospondin, type I, domain containing 4 −4.18 1.26E-04
A_23_P206920 NM_001040114 MYH11 Myosin, heavy chain 11, smooth muscle −4.13 1.26E-04
A_32_P154473 NM_004522 KIF5C Kinesin family member 5C −4.13 1.26E-04
A_23_P128362 NM_206819 MYBPC1 Myosin binding protein C, slow type −4.11 3.41E-04
A_23_P83381 NM_001143962 CAPN8 Calpain 8 −4.08 1.26E-04
A_23_P397208 NM_000848 GSTM2 Glutathione S-transferase mu 2 (muscle) −4.07 1.26E-04
A_23_P503072 NM_148672 CCL28 Chemokine (C-C motif) ligand 28 −4.03 1.26E-04
A_23_P143068 NM_024726 IQCA1 IQ motif containing with AAA domain 1 −4.01 1.26E-04
A_24_P829209 AK096334 LOC285944 Hypothetical protein LOC285944 −3.99 2.33E-04
A_23_P394246 GPR81 G protein-coupled receptor 81 −3.96 1.26E-04
A_24_P34186 NM_004010 DMD Dystrophin −3.96 1.26E-04
A_23_P303087 NM_002825 PTN Pleiotrophin −3.95 1.26E-04
A_24_P243749 NM_002612 PDK4 Pyruvate dehydrogenase kinase, isozyme 4 −3.94 1.26E-04
A_32_P39944 AK095791 N/A −3.82 1.26E-04
A_23_P217379 NM_033641 COL4A6 Collagen, type IV, α6 −3.8 1.26E-04
A_23_P407565 NM_001337 CX3CR1 Chemokine (C-X3-C motif) receptor 1 −3.76 1.26E-04
A_23_P373464 NM_002285 AFF3 AF4/FMR2 family, member 3 −3.75 1.26E-04
A_32_P183765 NM_005235 ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) −3.75 1.26E-04
A_23_P145514 NM_014432 IL20RA Interleukin 20 receptor, α −3.75 1.26E-04
A_24_P870620 NM_002825 PTN Pleiotrophin −3.74 2.33E-04
A_32_P154361 N/A N/A −3.73 1.26E-04
A_24_P330633 NM_000353 TAT Tyrosine aminotransferase −3.72 1.26E-04
A_23_P360777 NM_013960 NRG1 Neuregulin 1 −3.72 1.26E-04
A_23_P253982 NM_002141 HOXA4 Homeobox A4 −3.69 1.26E-04
A_32_P114475 N/A N/A −3.68 1.26E-04
A_32_P221774 BX099483 N/A −3.66 1.26E-04
A_23_P212608 NM_022131 CLSTN2 Calsyntenin 2 −3.66 2.33E-04
A_23_P254165 NM_021785 RAI2 Retinoic acid induced 2 −3.65 1.26E-04
A_24_P794447 NR_024430 LOC399959 Hypothetical LOC399959 −3.64 1.26E-04
A_23_P149517 NM_002644 PIGR Polymeric immunoglobulin receptor −3.64 1.26E-04
A_24_P904484 NR_024344 LOC283174 Hypothetical LOC283174 −3.62 1.26E-04
A_32_P194423 N/A N/A −3.62 1.26E-04
A_23_P371495 NM_175861 TMTC1 Transmembrane and tetratricopeptide repeat containing 1 −3.6 2.33E-04
A_23_P134162 NM_016356 DCDC2 Doublecortin domain containing 2 −3.58 1.26E-04
A_32_P232455 NM_178840 C1orf64 Chromosome 1 open reading frame 64 −3.58 1.26E-04
A_24_P318160 NM_014903 NAV3 Neuron navigator 3 −3.57 1.26E-04
A_23_P59388 NM_001723 DST Dystonin −3.56 1.26E-04
A_23_P399217 NM_153445 OR5P3 Olfactory receptor, family 5, subfamily P, member 3 −3.56 1.26E-04
A_23_P309739 NM_000125 ESR1 Estrogen receptor 1 −3.53 1.26E-04
A_24_P608007 AK022390 N/A −3.53 1.26E-04
A_23_P501538 NM_153631 HOXA3 Homeobox A3 −3.52 1.26E-04
A_24_P602871 NM_001030060 SAMD5 Sterile α motif domain containing 5 −3.52 1.26E-04
A_23_P136433 N/A N/A −3.51 1.26E-04
A_23_P30294 NM_001801 CDO1 Cysteine dioxygenase, type I −3.48 1.26E-04
A_23_P218928 NM_016613 FAM198B Family with sequence similarity 198, member B −3.47 1.26E-04
A_23_P154627 XM_002345419 TSHZ2 Teashirt zinc finger homeobox 2 −3.47 1.26E-04
A_23_P303833 NM_174934 SCN4B Sodium channel, voltage-gated, type IV, β −3.45 1.26E-04
A_24_P930088 XM_002342181 LOC100286909 Hypothetical protein LOC100286909 −3.45 1.26E-04
A_32_P81623 AA514833 N/A −3.42 1.26E-04
A_24_P923028 BC020707 TAT Tyrosine aminotransferase −3.41 1.26E-04
A_23_P58869 NR_002932 LOC442245 Glutathione S-transferase mu 2 pseudogene −3.4 1.26E-04
A_23_P2271 NM_198965 PTHLH Parathyroid hormone-like hormone −3.4 1.26E-04
A_32_P43664 −3.39 1.26E-04
A_32_P16007 NM_207355 POTEB POTE ankyrin domain family, member B −3.39 1.26E-04
A_23_P94840 NM_130897 DYNLRB2 Dynein, light chain, roadblock-type 2 −3.38 1.26E-04
A_24_P5153 NM_024817 THSD4 Thrombospondin, type I, domain containing 4 −3.38 1.26E-04
A_32_P223675 N/A N/A −3.37 1.26E-04
A_24_P904845 AK095791 N/A −3.37 1.26E-04
A_23_P403209 N/A N/A −3.36 1.26E-04
A_23_P215382 N/A N/A −3.35 3.41E-04
A_24_P209710 NM_004816 FAM189A2 Family with sequence similarity 189, member A2 −3.35 1.26E-04
A_23_P167168 NM_144646 IGJ Immunoglobulin J polypeptide, linker protein for immunoglobulin α and mu polypeptides −3.34 1.26E-04
A_24_P70183 NM_001040113 MYH11 Myosin, heavy chain 11, smooth muscle collagen, type XIV, α1 −3.32 1.26E-04
A_23_P216361 NM_021110 COL14A1 −3.32 1.26E-04
A_23_P113351 NM_004684 SPARCL1 SPARC-like 1 (hevin) −3.31 1.26E-04
A_32_P17145 N/A N/A −3.31 1.26E-04
A_23_P35414 NM_005398 PPP1R3C Protein phosphatase 1, regulatory (inhibitor) subunit 3C −3.29 1.26E-04
A_23_P31945 NM_033439 IL33 Interleukin 33 −3.27 1.26E-04
A_23_P204630 NM_021229 NTN4 Netrin 4 −3.26 1.26E-04
A_23_P501831 NM_032385 C5orf4 Chromosome 5 open reading frame 4 −3.26 1.26E-04
A_23_P200015 NM_174858 AK5 Adenylate kinase 5 −3.26 1.26E-04
A_24_P802145 NM_005544 IRS1 Insulin receptor substrate 1 −3.26 1.26E-04
A_24_P251969 NM_000800 FGF1 Fibroblast growth factor 1 (acidic) −3.24 1.26E-04
A_32_P228618 NM_001003793 RBMS3 RNA binding motif, single stranded interacting protein −3.23 1.26E-04
A_23_P125233 NM_001299 CNN1 Calponin 1, basic, smooth muscle −3.22 2.33E-04
A_23_P500998 NM_152739 HOXA9 Homeobox A9 −3.19 2.33E-04
A_23_P83838 NM_004056 CA8 Carbonic anhydrase VIII −3.19 1.26E-04
A_24_P911950 N/A N/A −3.17 1.26E-04
A_23_P159952 NM_018476 BEX1 Brain expressed, X-linked 1 −3.17 1.26E-04
A_23_P45185 NM_004469 FIGF c-fos induced growth factor (vascular endothelial growth factor D) −3.16 2.33E-04
A_23_P14083 NM_181847 AMIGO2 Adhesion molecule with Ig-like domain 2 −3.16 1.26E-04
A_24_P920366 N/A N/A −3.14 1.26E-04
A_24_P167668 NM_000428 LTBP2 Latent transforming growth factor β binding protein 2 −3.12 1.26E-04
A_32_P161033 BC043411 N/A −3.11 1.26E-04
A_23_P348159 NM_020388 DST Dystonin −3.11 1.26E-04
A_32_P89415 N/A N/A −3.1 1.26E-04
A_23_P165778 NM_024101 MLPH Melanophilin −3.08 1.26E-04
A_32_P168701 N/A N/A −3.07 3.41E-04
A_32_P78491 NM_004956 ETV1 ets variant 1 −3.06 1.26E-04
A_24_P87036 NM_018043 ANO1 Anoctamin 1, calcium activated chloride channel −3.06 1.26E-04
A_24_P912799 NM_003966 SEMA5A Sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A −3.06 1.26E-04
A_23_P315364 NM_002089 CXCL2 Chemokine (C-X-C motif) ligand 2 −3.05 1.26E-04
A_24_P71341 NM_001461 FMO5 Flavin containing monooxygenase 5 −3.05 2.33E-04
A_32_P199796 NM_004023 DMD Dystrophin −3.05 2.33E-04
A_32_P179998 NM_033053 DMRTC1 DMRT−like family C1 −3.04 1.26E-04
A_32_P17984 N/A N/A −3.04 1.26E-04
A_23_P138938 NM_000926 PGR Progesterone receptor −3.04 1.26E-04
A_23_P18559 NM_003866 INPP4B Inositol polyphosphate-4-phosphatase, type II, 105 kDa −3.03 1.26E-04
A_23_P124946 NM_153610 CMYA5 Cardiomyopathy associated 5 −3.03 1.26E-04
A_23_P212241 NM_006614 CHL1 Cell adhesion molecule with homology to L1CAM (close homolog of L1) −3.03 1.26E-04
A_23_P156402 NM_003551 NME5 Non-metastatic cells 5, protein expressed in (nucleoside-diphosphate kinase) −3.02 1.26E-04
A_23_P150053 NM_001613 ACTA2 Actin, α2, smooth muscle, aorta −3.02 1.26E-04
A_32_P58912 N/A N/A −3.02 1.26E-04
A_32_P216841 NM_145263 SPATA18 Spermatogenesis associated 18 homolog (rat) −3.01 2.33E-04
A_23_P257087 NM_002612 PDK4 Pyruvate dehydrogenase kinase, isozyme 4 −3.01 1.26E-04
A_23_P110686 NM_003714 STC2 Stanniocalcin 2 −3 1.26E-04
A_23_P369994 NM_004734 DCLK1 Doublecortin-like kinase 1 −2.99 2.33E-04
A_23_P422831 NM_004816 FAM189A2 Family with sequence similarity 189, member A2 −2.98 1.26E-04
A_24_P325992 NM_002310 LIFR Leukemia inhibitory factor receptor α −2.98 1.26E-04
A_23_P387000 NM_173683 XKR6 XK, Kell blood group complex subunit-related family, member 6 −2.98 3.41E-04
A_32_P83811 NM_001136570 FAM47E Family with sequence similarity 47, member E −2.98 1.26E-04
A_32_P44210 BX538299 N/A −2.97 1.26E-04
A_24_P918317 NM_015881 DKK3 Dickkopf homolog 3 (Xenopus laevis) −2.97 4.43E-04
A_23_P203957 NM_175861 TMTC1 Transmembrane and tetratricopeptide repeat containing 1 −2.96 3.41E-04
A_23_P30217 NM_052863 SCGB3A1 Secretoglobin, family 3A, member 1 −2.96 1.26E-04
A_23_P77066 NM_022807 SNRPN Small nuclear ribonucleoprotein polypeptide N −2.94 1.26E-04
A_32_P109242 AK055302 CSRNP3 Cysteine-serine-rich nuclear protein 3 −2.91 1.26E-04
A_24_P937265 N/A N/A −2.91 1.26E-04
A_32_P97968 N/A N/A −2.9 1.26E-04
A_32_P85684 AA069768 N/A −2.89 1.26E-04
A_23_P385067 NM_053277 CLIC6 Chloride intracellular channel 6 −2.89 4.43E-04
A_23_P82868 NM_000930 PLAT Plasminogen activator, tissue −2.88 1.26E-04
A_32_P108396 N/A N/A −2.88 1.26E-04
A_23_P148345 NM_194463 RNF128 Ring finger protein 128 −2.87 1.26E-04
A_24_P314477 NM_178012 TUBB2B Tubulin, β 2B −2.87 1.26E-04
A_24_P895836 N/A N/A −2.87 1.26E-04
A_23_P171074 NM_004867 ITM2A Integral membrane protein 2A −2.85 1.26E-04
A_23_P9135 NM_033655 CNTNAP3 Contactin associated protein-like 3 −2.85 4.43E-04
A_23_P372234 NM_001218 CA12 Carbonic anhydrase XII −2.83 1.26E-04
A_23_P393099 NM_003226 TFF3 Trefoil factor 3 (intestinal) −2.82 2.33E-04
A_23_P113701 NM_002607 PDGFA Platelet-derived growth factor α polypeptide −2.82 1.26E-04
A_23_P10995 NM_014483 RBMS3 RNA binding motif, single stranded interacting protein −2.82 1.26E-04
A_24_P269006 NM_001182 ALDH7A1 Aldehyde dehydrogenase 7 family, member A1 −2.81 1.26E-04
A_23_P415533 AK054879 N/A −2.81 1.26E-04
A_23_P216225 NM_004430 EGR3 Early growth response 3 −2.8 1.26E-04
A_24_P101282 N/A N/A −2.8 1.26E-04
A_32_P72541 N/A N/A −2.8 2.33E-04
A_24_P299474 NM_001122679 ODZ2 odz, odd Oz/ten-m homolog 2 (Drosophila) −2.8 1.26E-04
A_23_P416395 NM_003714 STC2 Stanniocalcin 2 −2.8 1.26E-04
A_23_P40415 NM_007038 ADAMTS5 ADAM metallopeptidase with thrombospondin type 1 motif, 5 −2.8 1.26E-04
A_32_P3545 XM_002345868 LOC100131504 Hypothetical LOC100131504 −2.79 4.43E-04
A_23_P106405 NM_002487 NDN Necdin homolog (mouse) −2.79 1.26E-04
A_23_P405129 NM_000428 LTBP2 Latent transforming growth factor β binding protein 2 −2.79 1.26E-04
A_24_P237804 NM_174981 POTED POTE ankyrin domain family, member D −2.78 1.26E-04
A_23_P89780 NM_198129 LAMA3 Laminin, α3 −2.78 1.26E-04
A_23_P213415 NM_003966 SEMA5A Sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A −2.77 3.41E-04
A_24_P397386 NM_002310 LIFR Leukemia inhibitory factor receptor α −2.77 1.26E-04
A_23_P73297 NM_004742 MAGI1 Membrane associated guanylate kinase, WW and PDZ domain containing 1 −2.77 1.26E-04
A_23_P165783 NM_024101 MLPH Melanophilin −2.76 1.26E-04
A_23_P212061 NM_007289 MME Membrane metallo-endopeptidase −2.76 1.26E-04
A_23_P75056 NM_001002295 GATA3 GATA binding protein 3 −2.76 1.26E-04
A_24_P748377 CR749529 −2.75 2.33E-04
A_24_P810476 NTRK3 Neurotrophic tyrosine kinase, receptor, type 3 −2.74 3.41E-04
A_32_P60606 AL713753 DKFZp667F0711 Hypothetical protein DKFZp667F0711 −2.74 1.26E-04
A_32_P200697 NM_181709 FAM101A Family with sequence similarity 101, member A −2.73 4.43E-04
A_24_P84220 NR_027995 LOC284232 Ankyrin repeat domain 20 family, member A2 pseudogene −2.73 1.26E-04
A_23_P157914 NM_153267 MAMDC2 MAM domain containing 2 −2.71 1.26E-04
A_24_P393596 N/A N/A −2.71 1.26E-04
A_32_P25419 N/A N/A −2.7 1.26E-04
A_24_P169873 N/A N/A −2.7 1.26E-04
A_24_P358534 N/A N/A −2.69 3.41E-04
A_32_P34750 AV702101 N/A −2.69 1.26E-04
A_32_P9941 NM_007191 WIF1 WNT inhibitory factor 1 −2.68 2.33E-04
A_23_P335143 U81001 SNRPN Small nuclear ribonucleoprotein polypeptide N −2.67 1.26E-04
A_23_P56855 NM_001137671 POTEC POTE ankyrin domain family, member C −2.67 1.26E-04
A_32_P59837 AK091914 N/A −2.65 1.26E-04
A_24_P737553 AK023774 N/A −2.65 2.33E-04
A_23_P204286 NM_000900 MGP Matrix Gla protein −2.65 1.26E-04
A_24_P725895 BE218249 N/A −2.63 1.26E-04
A_32_P4337 N/A N/A −2.63 1.26E-04
A_23_P154400 NM_001042467 MLPH Melanophilin −2.62 1.26E-04
A_23_P29800 NM_005602 CLDN11 Claudin 11 −2.61 1.26E-04
A_23_P156025 NM_033267 IRX2 Iroquois homeobox 2 −2.61 1.26E-04
A_32_P193091 N/A N/A −2.61 1.26E-04
A_23_P83857 NM_000240 MAOA Monoamine oxidase A −2.6 1.26E-04
A_32_P355396 NM_014844 TECPR2 Tectonin β-propeller repeat containing 2 −2.6 1.26E-04
A_32_P214565 BU928689 N/A −2.6 1.26E-04
A_24_P468950 AK021439 N/A −2.6 1.26E-04
A_24_P683583 N/A N/A −2.6 1.26E-04
A_23_P203558 NM_000518 HBB Hemoglobin, β −2.6 2.33E-04
A_32_P140153 N/A N/A −2.6 1.26E-04
A_32_P124461 AK129743 N/A −2.59 1.26E-04
A_23_P136026 AK128476 N/A −2.59 1.26E-04
A_23_P28295 NM_004525 LRP2 Low density lipoprotein-related protein 2 −2.59 4.43E-04
A_24_P586712 NM_198485 TPRG1 Tumor protein p63 regulated 1 −2.58 1.26E-04
A_23_P139500 NM_030762 BHLHE41 Basic helix-loop-helix family, member e41 −2.58 1.26E-04
A_23_P121480 NM_001004196 CD200 CD200 molecule −2.58 1.26E-04
A_23_P32577 NM_080759 DACH1 Dachshund homolog 1 (Drosophila) −2.58 1.26E-04
A_23_P315815 NM_004495 NRG1 Neuregulin 1 −2.58 1.26E-04
A_23_P93772 NM_019102 HOXA5 Homeobox A5 −2.58 1.26E-04
A_32_P150748 CR749529 N/A −2.58 1.26E-04
A_32_P204959 N/A N/A −2.58 1.26E-04
A_23_P363149 N/A N/A −2.57 4.43E-04
A_23_P41487 NM_015130 TBC1D9 TBC1 domain family, member 9 (with GRAM domain) −2.57 1.26E-04
A_23_P257296 NM_003226 TFF3 Trefoil factor 3 (intestinal) −2.56 3.41E-04
A_23_P250735 NM_175709 CBX7 Chromobox homolog 7 −2.56 1.26E-04
A_24_P189516 NM_001609 ACADSB acyl-coenzyme A dehydrogenase, short/branched chain −2.56 1.26E-04
A_23_P253012 NM_017577 GRAMD1C GRAM domain containing 1C −2.56 1.26E-04
A_24_P179244 XM_001723863 LOC100128979 Hypothetical protein LOC100128979 −2.55 1.26E-04
A_32_P117846 N/A N/A −2.55 1.26E-04
A_32_P42224 BX097190 N/A −2.55 2.33E-04
A_24_P119665 NM_001128933 SYNPO2 Synaptopodin 2 −2.54 1.26E-04
A_32_P105825 NM_001584 MPPED2 Metallophosphoesterase domain containing 2 −2.54 3.41E-04
A_24_P225679 NM_005544 IRS1 Insulin receptor substrate 1 −2.54 1.26E-04
A_32_P226907 N/A N/A −2.54 1.26E-04
A_23_P356581 NM_022370 ROBO3 Roundabout, axon guidance receptor, homolog 3 (Drosophila) −2.53 1.26E-04
A_32_P221096 AW015426 N/A −2.53 1.26E-04
A_23_P106016 NM_002742 PRKD1 Protein kinase D1 −2.52 1.26E-04
A_32_P210193 N/A N/A −2.52 1.26E-04
A_32_P38436 N/A N/A −2.52 1.26E-04
A_24_P512775 N/A N/A −2.52 1.26E-04
A_23_P151529 NR_023938 C14orf132 Chromosome 14 open reading frame 132 −2.52 1.26E-04
A_32_P235568 AK125221 N/A −2.52 1.26E-04
A_23_P71270 NM_001185 AZGP1 α-2-glycoprotein 1, zinc-binding −2.52 4.43E-04
A_24_P650425 N/A N/A Matrilin 2 −2.51 1.26E-04
A_23_P71328 NM_030583 MATN2 ras homolog gene family, member J −2.51 2.33E-04
A_24_P153803 NM_020663 RHOJ −2.51 1.26E-04
A_24_P912730 N/A N/A −2.51 1.26E-04
A_24_P347624 NM_022804 SNURF SNRPN upstream reading frame −2.5 1.26E-04
A_32_P52785 NM_015345 DAAM2 Dishevelled associated activator of morphogenesis 2 −2.5 3.41E-04
A_23_P61042 N/A N/A −2.5 1.26E-04
A_23_P67661 NM_001864 COX7A1 Cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) −2.49 1.26E-04
A_23_P213486 N/A PARP8 Poly(ADP-ribose) polymerase family, member 8 −2.49 1.26E-04
A_23_P18713 NM_004827 ABCG2 ATP-binding cassette, sub-family G (WHITE), member 2 −2.48 4.43E-04
A_23_P76658 NM_052818 N4BP2L1 NEDD4 binding protein 2-like 1 −2.48 1.26E-04
A_23_P96590 NM_014710 GPRASP1 G protein-coupled receptor associated sorting protein 1 −2.48 1.26E-04
A_24_P460763 AK022443 N/A −2.48 1.26E-04
A_23_P85672 NM_006610 MASP2 Mannan-binding lectin serine peptidase 2 −2.48 1.26E-04
A_24_P416489 N/A N/A −2.47 1.26E-04
A_24_P321525 NM_032918 RERG RAS-like, estrogen-regulated, growth inhibitor −2.47 1.26E-04
A_24_P256526 BC005914 SP2 Sp2 transcription factor −2.47 1.26E-04
A_24_P261417 NM_015881 DKK3 Dickkopf homolog 3 (Xenopus laevis) −2.47 1.26E-04
A_23_P98369 NM_000829 GRIA4 Glutamate receptor, ionotrophic, AMPA 4 −2.47 1.26E-04
A_23_P6818 NM_020163 SEMA3G Sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3G −2.46 3.41E-04
A_32_P100379 N/A N/A −2.46 1.26E-04
A_23_P30163 NR_026804 FLJ13197 Hypothetical FLJ13197 −2.46 1.26E-04
A_24_P206328 NM_005020 PDE1C Phosphodiesterase 1C, calmodulin-dependent 70 kDa −2.46 1.26E-04
A_24_P93948 AB210045 N/A −2.46 1.26E-04
A_32_P52414 N/A N/A −2.45 1.26E-04
A_23_P123228 NM_000111 SLC26A3 Solute carrier family 26, member 3 −2.45 1.26E-04
A_24_P666553 N/A N/A −2.45 1.26E-04
A_24_P916816 N/A N/A −2.44 1.26E-04
A_23_P134734 NM_017786 GOLSYN Golgi-localized protein −2.44 1.26E-04
A_24_P296772 NM_033256 PPP1R14A Protein phosphatase 1, regulatory (inhibitor) subunit 14A −2.43 1.26E-04
A_24_P267523 NM_144613 COX6B2 Cytochrome c oxidase subunit VIb polypeptide 2 (testis) −2.43 1.26E-04
A_23_P133517 NM_002310 LIFR Leukemia inhibitory factor receptor α −2.43 1.26E-04
A_24_P787680 N/A N/A −2.43 1.26E-04
A_32_P52829 N/A N/A −2.43 3.41E-04
A_23_P162047 NM_015881 DKK3 Dickkopf homolog 3 (Xenopus laevis) −2.43 1.26E-04
A_32_P185140 BX648171 TPM1 Tropomyosin 1 (α) −2.43 1.26E-04
A_24_P319892 NM_198274 SMYD1 SET and MYND domain containing 1 −2.43 1.26E-04
A_24_P226322 NM_031469 SH3BGRL2 SH3 domain binding glutamic acid-rich protein like 2 −2.42 1.26E-04
A_23_P86012 NM_001017402 LAMB3 Laminin, β3 −2.42 1.26E-04
A_23_P62255 NM_005314 GRPR Gastrin-releasing peptide receptor −2.41 1.26E-04
A_24_P141520 N/A N/A −2.41 2.33E-04
A_23_P114883 NM_002023 FMOD Fibromodulin −2.41 1.26E-04
A_23_P300033 NM_006206 PDGFRA Platelet-derived growth factor receptor, α polypeptide −2.41 2.33E-04
A_24_P108311 NM_015277 NEDD4L Neural precursor cell expressed, developmentally downregulated 4-like −2.41 1.26E-04
A_23_P345746 NM_199261 TPTE Transmembrane phosphatase with tensin homology −2.41 1.26E-04
A_23_P418083 NM_181714 LCA5 Leber congenital amaurosis 5 −2.41 1.26E-04
A_32_P208341 N/A N/A −2.41 1.26E-04
A_24_P930337 N/A N/A −2.41 1.26E-04
A_24_P915095 NM_017577 GRAMD1C GRAM domain containing 1C −2.4 1.26E-04
A_32_P4792 AK057820 N/A −2.4 1.26E-04
A_24_P82032 NM_020663 RHOJ ras homolog gene family, member J −2.39 2.33E-04
A_23_P204296 NM_032918 RERG RAS-like, estrogen-regulated, growth inhibitor −2.38 1.26E-04
A_24_P920712 N/A N/A −2.38 2.33E-04
A_24_P401185 NM_001042784 CCDC158 Coiled-coil domain containing 158 −2.38 1.26E-04
A_32_P109604 XM_001715342 LOC100132733 Similar to FLJ00310 protein −2.37 1.26E-04
A_24_P131173 NM_024709 C1orf115 Chromosome 1 open reading frame 115 −2.37 2.33E-04
A_24_P64241 NM_001012421 ANKRD20A2 Ankyrin repeat domain 20 family, member A2 −2.37 1.26E-04
A_32_P58437 N/A N/A −2.37 1.26E-04
A_24_P602348 N/A N/A −2.37 1.26E-04
A_24_P135856 NM_016124 RHD Rh blood group, D antigen −2.37 1.26E-04
A_23_P333038 NM_025145 C10orf79 Chromosome 10 open reading frame 79 −2.37 2.33E-04
A_23_P352266 NM_000633 BCL2 B-cell CLL/lymphoma 2 −2.36 1.26E-04
A_23_P207699 NM_016835 MAPT Microtubule-associated protein tau −2.36 1.26E-04
A_23_P392529 NR_027270 C21orf81 Ankyrin repeat domain 20 family, member A3 pseudogene −2.36 1.26E-04
A_23_P904 NM_024603 BEND5 BEN domain containing 5 −2.36 1.26E-04
A_23_P115785 NM_145235 FANK1 Fibronectin type III and ankyrin repeat domains 1 −2.35 1.26E-04
A_32_P146844 N/A N/A −2.35 1.26E-04
A_23_P26865 NM_002470 MYH3 Myosin, heavy chain 3, skeletal muscle, embryonic −2.35 1.26E-04
A_32_P100641 XM_001714998 LOC100128139 Hypothetical LOC100128139 −2.35 2.33E-04
A_24_P930727 AK091677 N/A −2.35 1.26E-04
A_23_P406341 NM_001001936 AFAP1L2 Actin filament associated protein 1-like 2 −2.35 1.26E-04
A_24_P54863 NM_152400 C4orf32 Chromosome 4 open reading frame 32 −2.34 1.26E-04
A_23_P133120 NM_018342 TMEM144 Transmembrane protein 144 −2.34 1.26E-04
A_32_P86705 BC040577 N/A −2.34 1.26E-04
A_24_P833256 N/A N/A −2.33 1.26E-04
A_23_P401106 NM_002599 PDE2A Phosphodiesterase 2A, cGMP-stimulated −2.33 1.26E-04
A_24_P102119 AF264623 N/A −2.33 1.26E-04
A_23_P358714 NM_020775 KIAA1324 KIAA1324 −2.32 1.26E-04
A_32_P162494 N/A N/A −2.32 3.41E-04
A_23_P326931 NM_145170 TTC18 Tetratricopeptide repeat domain 18 −2.32 1.26E-04

N/A, not annotated; P-value, Benjamini-Hochberg false discovery rate of random permutation test; log fold change, between groups. Gene symbol, accession number and gene name were exported from GeneSpring (from the NCBI databases).

Genes specifically expressed in TNBC, but not expressed in normal human vital organs.

Probe ID Accession no. Symbol Gene name Fold change (log) P-value
A_23_P118834 NM_001067 TOP2A Topoisomerase (DNA) IIα 170 kDa 4.76 1.26E-04
A_32_P119154 BE138567 N/A 4.75 1.26E-04
A_23_P35219 NM_002497 NEK2 NIMA (never in mitosis gene a)-related kinase 2 4.67 1.26E-04
A_23_P166360 NM_206956 PRAME Preferentially expressed antigen in melanoma 4.64 1.26E-04
A_24_P332314 NM_198947 FAM111B Family with sequence similarity 111, member B 4.63 1.26E-04
A_24_P413884 NM_001809 CENPA Centromere protein A 4.59 1.26E-04
A_23_P68610 NM_012112 TPX2 TPX2, microtubule-associated, homolog (Xenopus laevis) 4.58 1.26E-04
A_23_P401 NM_016343 CENPF Centromere protein F, 350/400 ka (mitosin) 4.44 1.26E-04
A_23_P57379 NM_003504 CDC45L CDC45 cell division cycle 45-like (S. cerevisiae) 4.44 1.26E-04
A_23_P356684 NM_018685 ANLN Anillin, actin binding protein 4.29 1.26E-04
A_23_P52017 NM_018136 ASPM asp (abnormal spindle) homolog, microcephaly associated (Drosophila) 4.17 1.26E-04
A_32_P199884 NM_032132 HORMAD1 HORMA domain containing 1 4.13 2.33E-04
A_23_P259586 NM_003318 TTK TTK protein kinase 4.09 1.26E-04
A_23_P200310 NM_017779 DEPDC1 DEP domain containing 1 4.08 1.26E-04
A_23_P115872 NM_018131 CEP55 Centrosomal protein 55 kDa 4.03 1.26E-04
A_24_P911179 NM_018136 ASPM asp (abnormal spindle) homolog, microcephaly associated (Drosophila) 4.02 1.26E-04
A_24_P96780 NM_016343 CENPF Centromere protein F, 350/400 ka (mitosin) 3.92 1.26E-04
A_24_P14156 NM_006101 NDC80 NDC80 homolog, kinetochore complex component (S. cerevisiae) 3.86 1.26E-04
A_23_P254733 NM_024629 MLF1IP MLF1 interacting protein 3.85 1.26E-04
A_23_P74115 NM_003579 RAD54L RAD54-like (S. cerevisiae) 3.84 1.26E-04
A_23_P50108 NM_006101 NDC80 NDC80 homolog, kinetochore complex component (S. cerevisiae) 3.84 1.26E-04
A_23_P155815 NM_022346 NCAPG Non-SMC condensin I complex, subunit G 3.82 1.26E-04
A_23_P51085 NM_020675 SPC25 SPC25, NDC80 kinetochore complex component, homolog (S. cerevisiae) 3.81 1.26E-04
A_32_P62997 NM_018492 PBK PDZ binding kinase 3.8 1.26E-04
A_23_P256956 NM_005733 KIF20A Kinesin family member 20A 3.79 1.26E-04
A_23_P212844 NM_006342 TACC3 Transforming, acidic coiled-coil containing protein 3 3.78 1.26E-04
A_24_P254705 NM_020394 ZNF695 Zinc finger protein 695 3.76 1.26E-04
A_23_P432352 NM_001017978 CXorf61 Chromosome X open reading frame 61 3.73 1.26E-04
A_23_P48669 NM_005192 CDKN3 Cyclin-dependent kinase inhibitor 3 3.71 1.26E-04
A_23_P94571 NM_004432 ELAVL2 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 2 (Hu antigen B) 3.67 1.26E-04
A_23_P150667 NM_031217 KIF18A Kinesin family member 18A 3.64 1.26E-04
A_32_P68525 BC035392 N/A 3.58 1.26E-04
A_24_P319613 NM_002497 NEK2 NIMA (never in mitosis gene a)-related kinase 2 3.53 1.26E-04
A_23_P10385 NM_016448 DTL Denticleless homolog (Drosophila) 3.53 1.26E-04
A_23_P94422 NM_014791 MELK Maternal embryonic leucine zipper kinase 3.5 1.26E-04
A_23_P340909 BC013418 SKA3 Spindle and kinetochore associated complex subunit 3 3.48 1.26E-04
A_23_P124417 NM_004336 BUB1 Budding uninhibited by benzimidazoles 1 homolog (yeast) 3.47 1.26E-04
A_24_P257099 NM_018410 HJURP Holliday junction recognition protein 3.43 1.26E-04
A_23_P74349 NM_145697 NUF2 NUF2, NDC80 kinetochore complex component, homolog (S. cerevisiae) 3.36 1.26E-04
A_24_P302584 NM_003108 SOX11 SRY (sex determining region Y)-box 11 3.36 4.43E-04
A_24_P68088 NR_002947 TCAM1 Testicular cell adhesion molecule 1 homolog (mouse) 3.35 2.33E-04
A_24_P366033 NM_018098 ECT2 Epithelial cell transforming sequence 2 oncogene 3.34 1.26E-04
A_23_P93258 NM_003537 HIST1H3B Histone cluster 1, H3b 3.33 1.26E-04
A_23_P149668 NM_014875 KIF14 Kinesin family member 14 3.29 1.26E-04
A_23_P34325 NM_033300 LRP8 Low density lipoprotein receptor-related protein 8, apolipoprotein E receptor 3.28 1.26E-04
A_32_P56154 N/A N/A 3.28 1.26E-04
A_23_P138507 NM_001786 CDC2 Cell division cycle 2, G1→S and G2→M 3.24 1.26E-04
A_23_P49972 NM_001254 CDC6 Cell division cycle 6 homolog (S. cerevisiae) 3.22 1.26E-04
A_24_P306896 XR_040656 LOC283711 Hypothetical protein LOC283711 3.22 1.26E-04
A_23_P44684 NM_018098 ECT2 Epithelial cell transforming sequence 2 oncogene 3.21 1.26E-04
A_23_P100344 NM_014321 ORC6L Origin recognition complex, subunit 6 like (yeast) 3.2 1.26E-04
A_23_P163481 NM_001211 BUB1B Budding uninhibited by benzimidazoles 1 homolog β (yeast) 3.17 1.26E-04
A_32_P87849 N/A N/A 3.16 1.26E-04
A_24_P397107 NM_001789 CDC25A Cell division cycle 25 homolog A (S. pombe) 3.15 1.26E-04
A_23_P209200 NM_001238 CCNE1 Cyclin E1 3.15 1.26E-04
A_32_P16625 N/A N/A 3.15 1.26E-04
A_24_P37903 N/A LOX Lysyl oxidase 3.12 1.26E-04
A_24_P313504 NM_005030 PLK1 Polo-like kinase 1 (Drosophila) 3.07 1.26E-04
A_23_P252292 NM_006733 CENPI Centromere protein I 3.04 1.26E-04
A_23_P161474 NM_182751 MCM10 Minichromosome maintenance complex component 10 2.99 1.26E-04
A_23_P253762 N/A N/A 2.94 1.26E-04
A_24_P225534 NM_017821 RHBDL2 Rhomboid, veinlet-like 2 (Drosophila) 2.94 1.26E-04
A_24_P412088 NM_182751 MCM10 Minichromosome maintenance complex component 10 2.94 1.26E-04
A_32_P109296 NM_152259 C15orf42 Chromosome 15 open reading frame 42 2.91 1.26E-04
A_24_P76521 AK056691 GSG2 Germ cell associated 2 (haspin) 2.83 1.26E-04
A_23_P126212 NM_022111 CLSPN Claspin homolog (Xenopus laevis) 2.83 1.26E-04
A_23_P60120 NM_031415 GSDMC Gasdermin C 2.81 2.33E-04
A_24_P902509 NM_018193 FANCI Fanconi anemia, complementation group I 2.8 1.26E-04
A_23_P155969 NM_014264 PLK4 Polo-like kinase 4 (Drosophila) 2.79 1.26E-04
A_32_P183218 NM_153695 ZNF367 Zinc finger protein 367 2.77 1.26E-04
A_23_P46118 NM_001821 CHML Choroideremia-like (Rab escort protein 2) 2.76 2.33E-04
A_23_P327643 N/A N/A 2.75 1.26E-04
A_23_P215976 NM_057749 CCNE2 Cyclin E2 2.72 2.33E-04
A_32_P151800 NM_207418 FAM72D Family with sequence similarity 72, member D 2.7 1.26E-04
A_23_P34788 NM_006845 KIF2C Kinesin family member 2C 2.7 1.26E-04
A_23_P133956 NM_002263 KIFC1 Kinesin family member C1 2.69 1.26E-04
A_23_P88630 NM_000057 BLM Bloom syndrome, RecQ helicase-like 2.68 1.26E-04
A_24_P276102 NM_183404 RBL1 Retinoblastoma-like 1 (p107) 2.68 1.26E-04
A_23_P23303 NM_003686 EXO1 Exonuclease 1 2.67 1.26E-04
A_23_P88691 NM_000745 CHRNA5 Cholinergic receptor, nicotinic, α5 2.67 1.26E-04
A_32_P72341 NM_173084 TRIM59 Tripartite motif-containing 59 2.62 1.26E-04
A_24_P227091 NM_004523 KIF11 Kinesin family member 11 2.61 1.26E-04
A_23_P136805 NM_014783 ARHGAP11A Rho GTPase activating protein 11A 2.6 1.26E-04
A_23_P63402 NM_013296 GPSM2 G-protein signaling modulator 2 (AGS3-like, C. elegans) 2.6 1.26E-04
A_23_P35871 NM_024680 E2F8 E2F transcription factor 8 2.58 1.26E-04
A_23_P207307 N/A N/A 2.58 1.26E-04
A_24_P399888 NM_001002876 CENPM Centromere protein M 2.58 1.26E-04
A_23_P155989 NM_022145 CENPK Centromere protein K 2.57 1.26E-04
A_23_P411335 NM_152524 SGOL2 Shugoshin-like 2 (S. pombe) 2.54 1.26E-04
A_23_P43484 NM_058197 CDKN2A Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 2.52 1.26E-04
A_32_P28704 N/A N/A 2.52 1.26E-04
A_24_P351466 NM_020890 KIAA1524 KIAA1524 2.5 1.26E-04
A_24_P334248 NM_014996 PLCH1 Phospholipase C, eta 1 2.48 1.26E-04
A_23_P88331 NM_014750 DLGAP5 Discs, large (Drosophila) homolog-associated protein 5 2.47 1.26E-04
A_32_P31021 N/A N/A 2.46 1.26E-04
A_23_P361419 NM_018369 DEPDC1B DEP domain containing 1B 2.45 1.26E-04
A_23_P397341 NM_152341 PAQR4 Progestin and adipoQ receptor family member IV 2.42 1.26E-04
A_23_P140316 NM_001099652 GPR137C G protein-coupled receptor 137C 2.42 1.26E-04
A_23_P217049 NM_014286 FREQ Frequenin homolog (Drosophila) 2.41 2.33E-04
A_32_P35839 N/A N/A 2.4 1.26E-04
A_24_P857404 NM_001093725 MEX3A mex-3 homolog A (C. elegans) 2.4 1.26E-04
A_24_P323598 NM_001017420 ESCO2 Establishment of cohesion 1 homolog 2 (S. cerevisiae) 2.36 1.26E-04
A_23_P112673 NM_017975 ZWILCH Zwilch, kinetochore associated, homolog (Drosophila) 2.33 1.26E-04
A_24_P296254 NM_014783 ARHGAP11A Rho GTPase activating protein 11A 2.32 1.26E-04

N/A, not annotated; P-value, Benjamini-Hochberg false discovery rate of random permutation test; log fold change, between groups. Gene symbol, accession number and gene name were exported from GeneSpring (from the NCBI databases).

Genes listed in cluster 1 and cluster 2.

No. of genes Genes
Cluster 1 (enrichment score, 29.90)
87 BLM, CKS1B, CKS2, CHEK1, E2F1, E2F2, E2F8, FANCA, FANCI, H2AFX, HORMAD1, HJURP, MAD2L1, NDC80, NEK2, NUF2, OIP5, PBK, RAD51, RAD54L, SPC25, TPX2, TTK, ZWINT ZWILCH, ANLN, ASPM, AURKA, BIRC5, BUB1, BUB1B, CASC5, CDC25A, CDC6, CDCA2, CDCA5, CDCA8, CENPA, CENPF, CEP55, CHAF1B, SKA3, C13orf34, CIT, CLSPN, CCNA2, CCNB1, CCNE1, CCNE2, CDKN2A, CDKN2C, CDKN3, DSCC1, DLGAP5, ESCO2, EXO1, FAM83D, GSG2, INHBA, KIF11, KIF14, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIFC1, LMNB1, MND1, NCAPG, NUSAP1, PTTG1, PLK1, PLK4, PKMYT1, PRC1, RBL1, SGOL2 SPAG5, STMN1, SMC4, TMSB15A, TOP2A, TACC3, TUBB3, UBE2C, UHRF1
Cluster 2 (enrichment score, 6.43)
45 ADAMTS5, MAMDC2, SPARCL1, WIF1, AZGP1, APOD, FIGF, CHL1, CCL28, CXCL2, COL4A6, COL14A1, COL17A1, CNTNAP3, DKK3, DST, FGF1, FMOD, HS3ST4, IGJ, IL33, LAMA3, LAMAB, LTBP2, LIFR, LRP2, MASP2, MATN2, MGP, NTN4, NRG1, PTHLH, PI15, PLAT, PDGFA, PTN, PIGR, PIP, SCGB1D1, SCGB1D2, SCGB3A1, SEMA3G, STC2, THSD4, TFF3

Genes enriched in cluster 1 and cluster 2 according to DAVID.