Identification of key genes in colorectal cancer using random walk with restart

Cui,Xiaofeng; Shen,Kexin; Xie,Zhongshi; Liu,Tongjun; Zhang,Haishan

doi:10.3892/mmr.2016.6058

Identification of key genes in colorectal cancer using random walk with restart

Authors:
- Xiaofeng Cui
- Kexin Shen
- Zhongshi Xie
- Tongjun Liu
- Haishan Zhang
View Affiliations

Affiliations: Department of Gastrointestinal Colorectal and Anal Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of General Surgery, Jilin University, Changchun, Jilin 130022, P.R. China
Published online on: December 19, 2016 https://doi.org/10.3892/mmr.2016.6058
Pages: 867-872

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

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

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

As the most common type of cancer and the second leading cause of cancer-associated mortality, colorectal cancer (CRC) has received increasing attention. The aim of the present study was to investigate the mechanisms of CRC by analyzing the microarray dataset, GSE32323. The GSE32323 dataset was downloaded from the Gene Expression Omnibus, and included 17 pairs of matched cancer and normal colorectal tissue samples. The differentially expressed genes (DEGs) were screened using the Linear Models for Microarray Data package and a search of CRC genes, also denoted as seed genes, was performed using the Online Mendelian Inheritance in Man database. Subsequently, the protein‑protein interaction (PPI) network was downloaded from the Search Tool for the Retrieval of Interacting Genes database and the sub‑network (CRC.PPI) of the DEGs and seed genes were obtained. In addition, the top 50 nodes with highest affinity scores in the CRC.PPI were identified using random walk with restart analysis. The potential functions of the DEGs included in the top 50 nodes were analyzed using the Database for Annotation, Visualization and Integrated Discovery online tool. Using the Drug Gene Interaction database, drug‑gene interaction analysis was performed to identify antineoplastic drug interacts with genes. A total of 1,640 DEGs between the CRC and normal samples were screened. The obtained seed genes included cyclin D1 (CCND1) and aurora kinase A (AURKA). The enriched functions for the 31 DEGs in the PPI network of the top 50 nodes were predominantly associated with cell cycle. The DEGs may function in CRC by interacting with other genes in the PPI network of the top 50 nodes, for example, DEP domain‑containing MTOR‑interacting protein (DEPTOR)‑CCND1, AURKA‑breast carcinoma amplified sequence‑1 (BCAS1), CCND1‑BCAS1, CCND1‑neural precursor cell expressed developmentally downregulated 9 (NEDD9) and CCND1‑mitogen‑activated protein kinase kinase 2 (MAP2K2). Only three DEGs (CCND1, AURKA and DEPTOR) had interactions with their corresponding antineoplastic drugs. Taken together, DEPTOR, AURKA, CCND1, BCAS1, NEDD9 and MAP2K2 may act in CRC.

View Figures

View References

1	Kune GA, Kune S and Watson LF: Colorectal cancer risk, chronic illnesses, operations and medications: Case control results from the melbourne colorectal cancer study. Cancer Res. 48:4399–4404. 1988.PubMed/NCBI
2	Majumdar SR, Fletcher RH and Evans AT: How does colorectal cancer present?; symptoms, duration, and clues to location. Am J Gastroenterol. 94:3039–3045. 1999. View Article : Google Scholar : PubMed/NCBI
3	Brenner H, Bouvier AM, Foschi R, Hackl M, Larsen IK, Lemmens V, Mangone L and Francisci S: Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: The EUROCARE study. Int J Cancer. 131:1649–1658. 2012. View Article : Google Scholar : PubMed/NCBI
4	Ferlay J, Parkin DM and Steliarova-Foucher E: Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 46:765–781. 2010. View Article : Google Scholar : PubMed/NCBI
5	Cianchi F, Cortesini C, Bechi P, Fantappiè O, Messerini L, Vannacci A, Sardi I, Baroni G, Boddi V, Mazzanti R and Masini E: Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology. 121:1339–1347. 2001. View Article : Google Scholar : PubMed/NCBI
6	Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, et al: Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res. 65:4562–4567. 2005. View Article : Google Scholar : PubMed/NCBI
7	Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J, Garner RC, Steele RJ and Wolf CR: Mutations in APC, Kirsten-ras, and p53-alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci USA. 99:9433–9438. 2002. View Article : Google Scholar : PubMed/NCBI
8	Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, Pretlow TP, Yang B, Akiyama Y, van Engeland M, et al: Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 36:417–422. 2004. View Article : Google Scholar : PubMed/NCBI
9	Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Powe NR and Feinberg AP: Loss of IGF2 imprinting: A potential marker of colorectal cancer risk. Science. 299:1753–1755. 2003. View Article : Google Scholar : PubMed/NCBI
10	Khamas A, Ishikawa T, Shimokawa K, Mogushi K, Iida S, Ishiguro M, Mizushima H, Tanaka H, Uetake H and Sugihara K: Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2′-deoxycytidine, microarray and gene expression profile. Cancer Genomics-Proteomics. 9:67–75. 2012.PubMed/NCBI
11	Gautier L, Cope L, Bolstad BM and Irizarry RA: affy-analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 20:307–315. 2004. View Article : Google Scholar : PubMed/NCBI
12	Smyth GK: Limma: Linear models for microarray dataBioinformatics and computational biology solutions using R and bioconductor. Springer; pp. 397–420. 2005, View Article : Google Scholar
13	Hamosh A, Scott AF, Amberger JS, Bocchini CA and McKusick VA: Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic acids Res. 33:D514–D517. 2005. View Article : Google Scholar : PubMed/NCBI
14	Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, et al: The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic acids Res. 39:D561–D568. 2011. View Article : Google Scholar : PubMed/NCBI
15	Fang H and Gough J: A disease-drug-phenotype matrix inferred by walking on a functional domain network. Mol Biosyst. 9:1686–1696. 2013. View Article : Google Scholar : PubMed/NCBI
16	Fang H and Gough J: The ‘dnet’ approach promotes emerging research on cancer patient survival. Genome Med. 6:642014. View Article : Google Scholar : PubMed/NCBI
17	Sherman BT, da W Huang, Tan Q, Guo Y, Bour S, Liu D, Stephens R, Baseler MW, Lane HC and Lempicki RA: DAVID Knowledgebase: A gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics. 8:4262007. View Article : Google Scholar : PubMed/NCBI
18	Hulsegge I, Kommadath A and Smits MA: Globaltest and GOEAST: Two different approaches for Gene Ontology analysis. BMC Proc. 3 Suppl 4:S102009. View Article : Google Scholar : PubMed/NCBI
19	Ogata H, Goto S, Sato K, Fujibuchi W, Bono H and Kanehisa M: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic acids Res. 27:29–34. 1999. View Article : Google Scholar : PubMed/NCBI
20	Griffith M, Griffith OL, Coffman AC, Weible JV, McMichael JF, Spies NC, Koval J, Das I, Callaway MB, Eldred JM, et al: DGIdb: Mining the druggable genome. Nat Methods. 10:1209–1210. 2013. View Article : Google Scholar : PubMed/NCBI
21	Lai1 EY, Chen ZG, Zhou X, Fan XR, Wang H, Lai PL, Su YC, Zhang BY, Bai XC and Li YF: DEPTOR Expression negatively correlates with mTORC1 activity and tumor progression in colorectal cancer. Asian Pac J Cancer Prev. 15:4589–4594. 2014. View Article : Google Scholar : PubMed/NCBI
22	Francipane MG and Lagasse E: mTOR pathway in colorectal cancer: An update. Oncotarget. 5:492014.PubMed/NCBI
23	Grünhage F, Jungck M, Lamberti C, Berg C, Becker U, Schulte-Witte H, Plassmann D, Rahner N, Aretz S, Friedrichs N, et al: Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes. Int J Colorectal Dis. 23:147–154. 2008. View Article : Google Scholar : PubMed/NCBI
24	Lewis RC, Bostick RM, Xie D, Deng Z, Wargovich MJ, Fina MF, Roufail WM and Geisinger KR: Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas. Cancer Res. 63:8549–8553. 2003.PubMed/NCBI
25	Zhang W, Gordon M, Press OA, Rhodes K, Vallböhmer D, Yang DY, Park D, Fazzone W, Schultheis A, Sherrod AE, et al: Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab. Pharmacogenet Genomics. 16:475–483. 2006. View Article : Google Scholar : PubMed/NCBI
26	Goos JA, Coupe VM, Diosdado B, Delis-Van Diemen PM, Karga C, Beliën JA, Carvalho B, van den Tol MP, Verheul HM, Geldof AA, et al: Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. Br J Cancer. 109:2445–2452. 2013. View Article : Google Scholar : PubMed/NCBI
27	Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, Schryver B, Flanagan P, Clairvoyant F, Ginther C, et al: A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 17:3052–3065. 1998. View Article : Google Scholar : PubMed/NCBI
28	Hermsen M, Postma C, Baak J, Weiss M, Rapallo A, Sciutto A, Roemen G, Arends JW, Williams R, Giaretti W, et al: Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology. 123:1109–1119. 2002. View Article : Google Scholar : PubMed/NCBI
29	Aust DE, Muders M, Köhler A, Schmidt M, Diebold J, Müller C, Löhrs U, Waldman FM and Baretton GB: Prognostic relevance of 20q13 gains in sporadic colorectal cancers: A FISH analysis. Scand J Gastroenterol. 39:766–772. 2004. View Article : Google Scholar : PubMed/NCBI
30	Nakao K, Mehta KR, Fridlyand J, Moore DH, Jain AN, Lafuente A, Wiencke JW, Terdiman JP and Waldman FM: High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization. Carcinogenesis. 25:1345–1357. 2004. View Article : Google Scholar : PubMed/NCBI
31	Postma C, Terwischa S, Hermsen MA, Van der Sijp JR and Meijer GA: Gain of chromosome 20q is an indicator of poor prognosis in colorectal cancer. Cell Oncol. 29:73–75. 2007.PubMed/NCBI
32	Carvalho B, Postma C, Mongera S, Hopmans E, Diskin S, van De Wiel MA, Van Criekinge W, Thas O, Matthäi A, Cuesta MA, et al: Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression. Gut. 58:79–89. 2009. View Article : Google Scholar : PubMed/NCBI
33	Sillars-Hardebol AH, Carvalho B, De Wit M, Postma C, Delis-van Diemen PM, Mongera S, Ylstra B, van De Wiel MA, Meijer GA and Fijneman RJ: Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression. Tumour Biol. 31:89–96. 2010. View Article : Google Scholar : PubMed/NCBI
34	Correa RG, De Carvalho AF, Pinheiro NA, Simpson AJ and De Souza SJ: NABC1 (BCAS1): Alternative splicing and downregulation in colorectal tumors. Genomics. 65:299–302. 2000. View Article : Google Scholar : PubMed/NCBI
35	Kim SH, Xia D, Kim SW, Holla V, Menter DG and DuBois RN: Human enhancer of filamentation 1 is a mediator of hypoxia-inducible factor-1alpha-mediated migration in colorectal carcinoma cells. Cancer Res. 70:4054–4063. 2010. View Article : Google Scholar : PubMed/NCBI
36	Singh MK, Cowell L, Seo S, O'Neill G and Golemis E: Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle. Cell Biochem Biophys. 48:54–72. 2007. View Article : Google Scholar : PubMed/NCBI
37	Xia D, Holla VR, Wang D, Menter DG and DuBois RN: HEF1 is a crucial mediator of the proliferative effects of prostaglandin E(2) on colon cancer cells. Cancer Res. 70:824–831. 2010. View Article : Google Scholar : PubMed/NCBI
38	Fang JY and Richardson BC: The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 6:322–327. 2005. View Article : Google Scholar : PubMed/NCBI
39	Yeh JJ, Routh ED, Rubinas T, Peacock J, Martin TD, Shen XJ, Sandler RS, Kim HJ, Keku TO and Der CJ: KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. Mol Cancer Ther. 8:834–843. 2009. View Article : Google Scholar : PubMed/NCBI