Open Access

High‑level SETD1B gene expression is associated with unfavorable prognosis in hepatocellular carcinoma

  • Authors:
    • Dong Chen
    • Tieling Li
    • Cheng Wang
    • Guanglin Lei
    • Ruilan Wang
    • Zhaohai Wang
    • Linxiang Yu
    • Jin Yan
    • Peirui Zhang
    • Xiliang Wang
    • Shaogeng Zhang
    • Penghui Yang
  • View Affiliations

  • Published online on: January 8, 2019     https://doi.org/10.3892/mmr.2019.9832
  • Pages: 1587-1594
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The SET domain‑containing 1B (SETD1B) gene is involved in multiple biological processes, including tumor development and progression. However, the role of SETD1B in hepatocellular carcinoma (HCC) is largely unexplored. The present study, examined the expression of SETD1B in patients with HCC and assessed its clinical significance. Reverse transcriptase quantitative polymerase chain reaction and western blot analysis results revealed that the expression levels of SETD1B mRNA and protein were significantly increased in HCC tumor tissues compared with the adjacent normal tissues. In addition, an analysis of the patient clinical factors indicated that increased levels of SETD1B expression were associated with tumor size, clinical stage and liver cirrhosis. Patients with HCC with decreased levels of SETD1B expression exhibited longer survival times compared with those with increased levels of SETD1B expression. In addition, Cox's regression analysis results implied that the upregulation of SETD1B was an independent prognostic marker in patients with HCC. Taken together, the results demonstrated that SETD1B is essential in the progression of HCC and may be used as a potential prognostic marker and therapeutic target in HCC.

Introduction

Hepatocellular carcinoma (HCC) is one of the leading human malignancies prevalent worldwide, and half of the incident cases each year occur in China (1,2). In general, the majority of patients with HCC are diagnosed in the clinic at a late stage of disease progression, and therefore do not have the opportunity for a surgical resection. At present, sorafenib and regorafenib are the only United States of America Food and Drug Administration-approved molecularly targeted drugs for patients with HCC (3). However, the efficacy of HCC treatments remains limited and unsatisfactory. Therefore, to improve the prognosis and quality of life of patients with HCC, novel early diagnostic biomarkers and therapeutic drug targets are urgently required.

SET domain-containing 1B (SETD1B), also known as KMT2G or Set1B, is an important component of the histone methyltransferase complex that generates trimethylated histone H3 at Lys4 and has been implicated in multiple biological processes (4). The SETD1B gene is located on chromosome 1q12 and encodes a 130-kDa protein with several functional domains. A previous study demonstrated that SETD1B associates with a 450-kDa complex that contains all five noncatalytic components of the SET domain containing 1A (SET1A) complex: CXXC finger protein 1, AT-rich interaction domain 4A, ASH2 like, histone lysine methyltransferase complex subunit, WD repeat domain 5 and WD repeat domain 82 (5). The mixed lineage leukemia (MLL) family of proteins, including MLL1-MLL4, SET1A and SETD1B, specifically methylates Lys4 of histone H3 and serves a vital role in the transcriptional regulation of genes (6). In our previous study, it was identified that SETD1B was the most frequently mutated gene in primary hepatic neuroendocrine tumor, and that one of the three SETD1B mutants, A1054del, promoted cell proliferation, migration and invasion (7). However, the underlying role of SETD1B in liver carcinogenesis was not addressed. Therefore, an investigation into the expression patterns of SETD1B and its clinical significance in the development and progression of HCC was warranted.

Materials and methods

Clinical samples

Fresh surgical tumor samples from 76 patients with HCC were collected from the Hepatobiliary Department of Beijing 302 Hospital (Beijing, China) between October 2013 and March 2018 and were examined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. For the immunohistochemical (IHC) analysis, paraffin-embedded HCC samples were collected between October 2013 and March 2015. The HCC tissues were fixed in 10% formalin for 24 h at room temperature, embedded in paraffin and cut into 4-µm sections. Within half an hour of isolation, HCC tissues and adjacent tissue samples were quickly placed into liquid nitrogen. Adjacent tissue samples were taken at a distance >3 cm from the cancer tissues. Written informed consent was obtained from the enrolled patients with HCC. The present study was approved by The Ethics Committee of Beijing 302 Hospital.

Cell lines and cell culture

The human liver cancer 97L and HCCLM3 cell lines and the normal human liver LO2 cell line used in the present study were obtained from the Experimental Center of Beijing 302 Hospital (Beijing, China). All these cell lines were maintained and in Dulbecco's modified Eagle's medium (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) supplemented with 10% fetal bovine serum (Gibco; Thermo Fisher Scientific, Inc.) and incubated at 37°C with 5% CO2.

RT-qPCR

Total RNA from the frozen tissue samples of 76 patients with HCC was extracted using TRIzol® reagent (Thermo Fisher Scientific, Inc.) according to the manufacturer's instructions. SETD1B expression levels were quantified by RT-qPCR methods conducted in an ABI 7500 instrument (Applied Biosystems; Thermo Fisher Scientific, Inc.) using the Maxima SYBR-Green RT-qPCR master mix (Thermo Fisher Scientific, Inc.) according to the protocol of the manufacturer. All experimental samples were normalized to a human GAPDH control. The sequences of the RT-PCR primers were as follows: SETD1B forward, 5′-CTGGGTCTACCATCCCTCCA-3′ and reverse, 5′-CTTCCGGAACTTGAGCTGGT-3′; GAPDH forward, 5′-CAGCCTCAAGATCATCAGCA-3′ and reverse, 5′-TGTGGTCATGAGTCCTTCCA-3′. The amplification procedure consisted of an initial denaturation at 95°C for 5 min, followed by 40 cycles of denaturation at 95°C for 15 sec, and annealing and extension at 60°C for 30 sec. The 2−ΔΔCq method was used to analyze SETD1B expression levels relative to the GAPDH control (8).

Western blot analysis

The total proteins were extracted from surgical samples from the patients with HCC using Tissue Protein Extraction Reagent (Pierce; Thermo Fisher Scientific, Inc.) and quantified using a Bicinchoninic Acid Protein Assay (Pierce; Thermo Fisher Scientific, Inc.). A total of 30 µg protein was loaded per lane. Proteins were separated by 12% SDS-PAGE and were subsequently transferred onto polyvinylidene fluoride (PVDF) membranes (EMD Millipore, Billerica, MA, USA) for western blot analysis. The PVDF membranes were incubated with a primary monoclonal anti-SETD1B antibody (cat. no. ab113984; Abcam, Cambridge, MA, USA; 1:500) at 2–8°C overnight and were subsequently incubated with a horseradish peroxidase (HRP)-conjugated secondary antibody (cat. no. RABHRP1; Sigma-Aldrich; Merck KGaA, Darmstadt, Germany; 1:1,000) for 1 h at room temperature. Targeted SETD1B protein bands were visualized using an enhanced chemiluminescence kit (Pierce; Thermo Fisher Scientific, Inc.). The primary antibody for β-actin (cat. no. 3700; Cell Signaling Technology, Inc., Danvers, MA, USA; 1:1,000) was used to as a loading control for the western blot analysis.

IHC staining

IHC experiments were conducted as previously described (9). The deparaffinized sections were boiled for 2.5 min in citrate buffer, pH 6.0. Endogenous peroxidase activity was blocked through incubation with a 3% hydrogen peroxide solution for 20 min at room temperature. Subsequently, the 4-µm sections were incubated for 24 h at 4°C with a primary monoclonal anti-SETD1B antibody (Abcam; cat. no. ab113984; 1:500) and subsequently with an HRP-labeled anti-rabbit immunoglobulin G secondary antibody (cat. no. AP101P; Sigma-Aldrich; Merck KGaA; 1:1,000) for 2 h at 37°C. The positive cells were analyzed in five distinct fields and images were captured under different magnifications using a light microscope (Olympus Corporation, Tokyo, Japan; magnification, ×100 and ×200).

Statistical analysis

Data are presented as the mean ± standard deviation. Statistical analyses were performed using the SPSS 20.0 software (IBM Corp., Armonk, NY, USA). The Wilcoxon test was used to determine SETD1B expression in HCC paired tissues. A paired t-test was used to compare SETD1B expression in RNA-Seq studies.

RNA-Seq data of 66 paired HCC samples were retrieved from The Cancer Genome Atlas (TCGA) Firehose pipeline on the Broad Institute website (http://gdac.broadinstitute.org/). Kaplan-Meier curves were conducted to analyze the associations between the SETD1B expression levels and the overall survival (OS) or disease-free survival (DFS) rates of the patients with HCC. Univariate and multivariate cox regression analysis were performed with the Cox proportional hazards regression model to determine the effects of prognostic factors on survival. P<0.05 was considered to indicate a statistically significant difference.

Results

SETD1B is upregulated in HCC samples and cell lines

To investigate the role of SETD1B in the development and progression of HCC, RT-qPCR was used to examine the SETD1B expression levels in 76 pairs of HCC tissues and adjacent nontumor tissue samples. As observed in Fig. 1, SETD1B levels were significantly upregulated in the HCC tissues compared with those in the adjacent normal tissues (P<0.001; Fig. 1A-B). To additionally confirm the overexpression of SETD1B in HCC tissues, 4 pairs of HCC and adjacent normal tissues were selected to evaluate the protein levels of SETD1B by western blot analysis. As expected, it was visually observed that the western blot analysis results were consistent with the RT-qPCR data (Fig. 1C). The expression levels of SETD1B in 2 human HCC cell lines (97L and HCCLM3) were also determined and upregulated SETD1B expression levels were observed in the HCC cell lines compared with that in LO2 cells (Fig. 1D). In addition, the SETD1B expression levels of 66 paired HCC samples in The Cancer Genome Atlas (TCGA) RNA-Seq data set were analyzed, and it was identified that SETD1B levels were also significantly increased in these samples (Fig. 1E). These results prompted additional investigation into the potential role of SETD1B in HCC carcinogenesis.

Upregulation of SETD1B in HCC tissues determined by IHC

Next, to additionally clarify whether SETD1B was upregulated at the protein level, IHC was performed to examine SETD1B expression in sections of paired HCC tissue samples. It was visually observed that SETD1B expression was primarily located in the nucleus and was markedly increased in the HCC cells compared to that in normal adjacent hepatocytes (Fig. 2). Taking together, it was concluded that SETD1B was upregulated in human HCC tissues at the mRNA and protein levels.

Association between SETD1B protein expression and the clinicopathological features of HCC

To additionally explore whether SETD1B expression in HCC tissues determined the clinical prognosis in patients with HCC, 76 patients with HCC were divided into high SETD1B and low SETD1B expression groups according to the mean value of the expression levels of SETD1B in HCC samples. As demonstrated in Table I, it was identified that high SETD1B expression was closely associated with tumor size (P<0.05), clinical tumor stage (P<0.01) and whether or not liver cirrhosis was present (P<0.05). By contrast, no association was observed between SETD1B expression and other parameters, including sex, age, the α-fetoprotein level, smoking status, drinking status, recurrence and portal vein tumor thrombus (PVTT) (P>0.05).

Table I.

Association between SETD1B expression and clinicopathological features in hepatocellular carcinoma.

Table I.

Association between SETD1B expression and clinicopathological features in hepatocellular carcinoma.

SETH1B expression

ParametersNo. of patientsLowHighP-value
Age, years
  <605831270.280
  ≥6018711
Sex
  Male6833350.455
  Female853
Tumor size, cm
  <54828200.028a
  ≥528919
AFP
  <202413110.622
  ≥20522527
Histological grade
  Well/moderate7034360.395
  Poor642
Clinical stage
  I–II5939200.007b
  III–IV17512
Number of tumors
  Single6330330.361
  Multiple1385
Alcohol consumption
  Yes3218140.353
  No442024
Smoking status
  Yes4220220.645
  No341816
Recurrence
  Yes2312110.803
  No532627
Portal vein tumor thrombus
  Yes4221210.896
  No341717
Microvascular invasion
  Yes6132290.387
  No1569
Liver cirrhosis
  Absent2716110.039a
  Present491732

{ label (or @symbol) needed for fn[@id='tfn1-mmr-19-03-1587'] } Results are expressed as the mean of 2−ΔΔCq values.

a P<0.05

b P<0.01. SETD1B, SET domain-containing 1B.

SETD1B expression and HCC patient survival

To additionally evaluate whether SETD1B expression exhibited prognostic potential for the OS of patients with HCC, the association between SETD1B expression and HCC patient survival rates was analyzed using Kaplan-Meier analyses. As indicated in Fig. 3, the 3-year OS rate of the 76 patients with HCC was 60%. In addition, the associations between SETD1B expression and the survival outcomes of the patients with HCC were investigated using on Kaplan-Meier analyses. The results suggested that an increased SETD1B expression level in HCC tissues was significantly associated with a decrease in OS (P=0.005; Fig. 3B) and DFS (P=0.036; Fig. 3C) during the 3-year follow-up period. In addition, survival benefits were observed in patients with a small tumor size (P=0.003), with an early clinical stage (P=0.041), without PVTT (P=0.043) and without liver cirrhosis (P=0.021). Multivariate Cox regression analysis revealed that SETD1B expression [relative risk (RR)=4.151; P=0.016], tumor size (RR=8.639; P=0.001) and clinical stage (RR=6.371; P=0.006) were independent prognostic markers for OS in patients with HCC (Table II), indicating that SETD1B is essential for the development, progression and outcomes of HCC.

Table II.

Univariate and multivariate cox regression analysis for overall survival in 76 patients with HCC.

Table II.

Univariate and multivariate cox regression analysis for overall survival in 76 patients with HCC.

Univariate regression analysisMultivariate regression analysis


VariableRRP-valueRRP-value
Age
  <601.453 1
  ≥60 0.4561.2960.625
Sex
  Male0.981 1
  Female 0.9561.0320.968
Tumor size (cm)1
  <5 cm6.138 1
  ≥5 cm 0.0038.6390.001
α-fetoprotein1
  <200.738 1
  ≥20 0.5360.6830.428
Histological grade1
  Well/moderate1.956 1
  Poor 0.3964.1750.096
Clinical stage1
  I–II5.42
  III–IV 0.0416.3710.006
Number of tumors1
  Single8.624 1
  Multiple 0.3616.7510.132
Alcohol consumption1
  Yes1.435 1
  No 0.4161.3690.652
Smoking status1
  Yes1.466 1
  No 0.4651.0960.725
Recurrence1
  Yes1.853 1
  No 0.6561.4960.854
Portal vein tumor thrombus1
  Yes1.493
  No 0.043
Microvascular invasion1
  Yes6.453 1
  No 2.4564.2960.625
Liver cirrhosis1
  Absent5.62
  Present 0.021
SETD1B expression1
  Low5.123 1
  High

[i] RR, relative risk; SETD1B, SET domain-containing 1B.

Discussion

To the best of our knowledge, the present study demonstrated for the first time that SETD1B expression is significantly increased in HCC tissues compared with that in adjacent normal tissues. Specifically, the increased expression of SETD1B in HCC was associated with tumor size, a more advanced clinical stage and the development of liver cirrhosis. In addition, it was identified that increased SETD1B expression was associated with decreased OS rates. Furthermore, Cox regression analysis demonstrated that SETD1B is an independent predictive marker for the prognosis of HCC. This result was additionally validated with a larger cohort of HCC samples from the TCGA database. These data suggested that SETD1B may serve critical roles in HCC development and progression, and monitoring SETD1B levels may have potential clinical applications. However, insights into the mechanism of how overexpression, not mutation, contributes to a poor outcome in HCC require additional investigation.

SETD1B encodes a histone H3 Lysine 4 (H3K4)-methyltransferase and is a component of the SET1 complex (SET1C)/complex proteins associated with Set1 complex, which participates in a number of biological processes (1013). For example, a previous study demonstrated that tumor cells use the SETD1B-Histone H3 lysine 4 trimethylation (H3K4me3) epigenetic axis to bypass the normal role of interferon regulatory factor 8 expression in activating inducible nitric oxide synthase (iNOS) expression in myeloid-derived suppressor cells under pathological conditions (14). Setd1b deficiency causes female sterility in mice and serves as a maternal effect gene by regulating the oocyte gene expression program (15). The MLL/Setd1b methyltransferase is required for Spemann's organizer gene activation in Xenopus (16). A frameshift mutation in the histone methylation-associated gene SETD1B results in its regional heterogeneity in gastric and colorectal cancer with high microsatellite instability (17). Song et al (18) identified that SETD1B, as one of the important histone regulator genes, is frequently altered in esophageal squamous cell carcinoma. The molecular mechanisms for SETD1B function in carcinogenesis and cancer progression have not been clearly elucidated. Although a role of SETD1B as an oncogene in HCC has been suggested in the present study, the underlying mechanisms of increased SETD1B expression in HCC progression remain largely elusive. For example, to verify that the significance of SETD1B in HCC is based on epigenetic modification, subsequent studies with chromatin immunoprecipitation PCR in HCC tissues are required to assess whether the H3K3 modifications are enhanced around the critical transcription factor genes that have been suggested to significantly contribute to HCC pathogenesis. In addition, a limited number of HCC tissue samples were analyzed in the present study, and SETD1B expression levels require confirmation with larger cohorts of HCC clinical samples. Whether SETD1B may also be detected in the plasma or even in circulating exosomes and whether the circulating SETD1B is also associated with HCC development are also key issues to consider. Therefore, the role of SETD1B in HCC progression requires investigation, and will be a focus in subsequent studies.

SETD1B catalyzes the methylation of H3K4, and several other enzymes including SETD1A, histone-lysine N-methyltransferase SETD7, MLL1-4 and histone-lysine N-methyltransferase SMYD (SMYD) 1–3 catalyze the same reaction (11). The level of H3K4 methylation affects gene transcription, but this level depends not only on the activity of these methyltransferases but also on that of demethylases, or ‘erasers’ (19). In humans, the erasers for H3K4me are lysine-specific histone demethylase (LSD)1-2, lysine-specific demethylase 5A-D and ribosomal oxygenase 1. For example, a previous study described the role of the SMYD3 histone methyltransferase in tumorigenesis and whether the effects are local or global (19). JARID1B promotes metastasis and the epithelial-mesenchymal transition via phosphatase and tensin homolog/protein kinase B signaling in HCC cells (20). While it is true that the role of SETD1B in HCC has not been described at present, those other ‘writers’ or ‘erasers’ also affect the level of the same epigenetic marker, H3K4me3, that results from SETD1B action. It has been suggested that a high level of JARID1B expression was associated with decreased OS in patients with HCC (20). Considering that SETD1B and JARID1B induce opposite effects on the level of H3K4me3, it was hypothesized that the reason for these results is a small sample size and individual differences in the patients with HCC.

In summary, the results of the present study reveal that SETD1B expression is markedly upregulated in HCC tissues, and is associated with a poor prognosis in patients with HCC. The overexpression of SETD1B was associated with tumor size, clinical stage and the presence of liver cirrhosis. These data demonstrate that SETD1B has potential as a predictive marker for prognosis and as a therapeutic drug target for HCC.

Acknowledgements

Not applicable.

Funding

The present study was supported by a grant from the National Natural Science Foundation of China (grant no. 81601860).

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Authors' contributions

DC, CW, GL, RW, ZW and LY performed the experiments. DC, TL, PZ and JY gathered clinical samples and performed the clinical analysis. XW, SZ and PY designed the study and wrote the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Informed consent was obtained from the enrolled patients. The present study was approved by the Ethics Committee of Beijing 302 Hospital (Beijing, China).

Patient consent for publication

Written informed consent was obtained from the enrolled patients.

Competing interests

The authors declare that they have no competing interests.

References

1 

Yang Y, Zhou Y, Hou J, Bai C, Li Z, Fan J, Ng IOL, Zhou W, Sun H, Dong Q, et al: Hepatic IFIT3 predicts interferon-α therapeutic response in patients of hepatocellular carcinoma. Hepatology. 66:152–166. 2017. View Article : Google Scholar : PubMed/NCBI

2 

El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, et al: Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial. J Clin Oncol. 31:4067–4075. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Lee JH, Tate CM, You JS and Skalnik DG: Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex. J Biol Chem. 282:13419–13428. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Duncan EM, Chitsazan AD, Seidel CW and Alvarado AS: Set1 and MLL1/2 target distinct sets of functionally different genomic loci in vivo. Cell Rep. 17:9302016. View Article : Google Scholar : PubMed/NCBI

6 

Li Y, Han J, Zhang Y, Cao F, Liu Z, Li S, Wu J, Hu C, Wang Y, Shuai J, et al: Structural basis for activity regulation of MLL family methyltransferases. Nature. 530:447–452. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Zhang BL, Ji X, Yu LX, Gao Y, Xiao CH, Liu J, Zhao DX, Le Y, Diao GH, Sun JY, et al: Somatic mutation profiling of liver and biliary cancer by targeted next generation sequencing. Oncol Lett. 16:6003–6012. 2018.PubMed/NCBI

8 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Li J, Wu H, Li W, Yin L, Guo S, Xu X, Ouyang Y, Zhao Z, Liu S, Tian Y, et al: Downregulated miR-506 expression facilitates pancreatic cancer progression and chemoresistance via SPHK1/Akt/NF-κB signaling. Oncogene. 35:5501–5514. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Davie JR, Xu W and Delcuve GP: Histone H3K4 trimethylation: Dynamic interplay with pre-mRNA splicing. Biochem Cell Biol. 94:1–11. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Yang W and Ernst P: Distinct functions of histone H3, lysine 4 methyltransferases in normal and malignant hematopoiesis. Curr Opin Hematol. 24:322–328. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Hiraide T, Nakashima M, Yamoto K, Fukuda T, Kato M, Ikeda H, Sugie Y, Aoto K, Kaname T, Nakabayashi K, et al: De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism. Hum Genet. 137:95–104. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Schmidt K, Zhang Q, Tasdogan A, Petzold A, Dahl A, Arneth BM, Slany R, Fehling HJ, Kranz A, Stewart AF and Anastassiadis K: The H3K4 methyltransferase Setd1b is essential for hematopoietic stem and progenitor cell homeostasis in mice. Elife. 7:e271572018. View Article : Google Scholar : PubMed/NCBI

14 

Redd PS, Ibrahim ML, Klement JD, Sharman SK, Paschall AV, Yang D, Nayak-Kapoor A and Liu K: SETD1B activates iNOS expression in myeloid-derived suppressor cells. Cancer Res. 77:2834–2843. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Brici D, Zhang Q, Reinhardt S, Dahl A, Hartmann H, Schmidt K, Goveas N, Huang J, Gahurova L, Kelsey G, et al: Setd1b, encoding a histone 3 lysine 4 methyltransferase, is a maternal effect gene required for the oogenic gene expression program. Development. 144:2606–2617. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Lin H, Min Z and Tao Q: The MLL/Setd1b methyltransferase is required for the Spemann's organizer gene activation in Xenopus. Mech Dev. 142:1–9. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Choi YJ, Oh HR, Choi MR, Gwak M, An CH, Chung YJ, Yoo NJ and Lee SH: Frameshift mutation of a histone methylation-related gene SETD1B and its regional heterogeneity in gastric and colorectal cancers with high microsatellite instability. Hum Pathol. 45:1674–1681. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Song Y, Li L, Ou Y, Gao Z, Li E, Li X, Zhang W, Wang J, Xu L, Zhou Y, et al: Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 509:91–95. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Medjkane S, Cock-Rada A and Weitzman JB: Role of the SMYD3 histone methyltransferase in tumorigenesis: Local or global effects? Cell Cycle. 11:18652012. View Article : Google Scholar : PubMed/NCBI

20 

Tang B, Qi G, Tang F, Yuan S, Wang Z, Liang X, Li B, Yu S, Liu J, Huang Q, et al: JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells. Oncotarget. 6:12723–12739. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

March-2019
Volume 19 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chen D, Li T, Wang C, Lei G, Wang R, Wang Z, Yu L, Yan J, Zhang P, Wang X, Wang X, et al: High‑level SETD1B gene expression is associated with unfavorable prognosis in hepatocellular carcinoma. Mol Med Rep 19: 1587-1594, 2019
APA
Chen, D., Li, T., Wang, C., Lei, G., Wang, R., Wang, Z. ... Yang, P. (2019). High‑level SETD1B gene expression is associated with unfavorable prognosis in hepatocellular carcinoma. Molecular Medicine Reports, 19, 1587-1594. https://doi.org/10.3892/mmr.2019.9832
MLA
Chen, D., Li, T., Wang, C., Lei, G., Wang, R., Wang, Z., Yu, L., Yan, J., Zhang, P., Wang, X., Zhang, S., Yang, P."High‑level SETD1B gene expression is associated with unfavorable prognosis in hepatocellular carcinoma". Molecular Medicine Reports 19.3 (2019): 1587-1594.
Chicago
Chen, D., Li, T., Wang, C., Lei, G., Wang, R., Wang, Z., Yu, L., Yan, J., Zhang, P., Wang, X., Zhang, S., Yang, P."High‑level SETD1B gene expression is associated with unfavorable prognosis in hepatocellular carcinoma". Molecular Medicine Reports 19, no. 3 (2019): 1587-1594. https://doi.org/10.3892/mmr.2019.9832