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Journal of Cancer Research and Clinical Oncology

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01-12-2017 | Original Article – Clinical Oncology

Identification of prognostic markers of high grade prostate cancer through an integrated bioinformatics approach

Authors: Hai Huang, Qin Zhang, Chen Ye, Jian-Min Lv, Xi Liu, Lu Chen, Hao Wu, Lei Yin, Xin-Gang Cui, Dan-Feng Xu, Wen-Hui Liu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2017

Abstract

Purpose

Prostate cancer is one of the leading causes of cancer death for male. In the present study, we applied an integrated bioinformatics approach to provide a novel perspective and identified some hub genes of prostate cancer.

Method

Microarray data of fifty-nine prostate cancer were downloaded from Gene Expression Omnibus. Gene Ontology and pathway analysis were applied for differentially expressed genes between high and low grade prostate cancer. Weighted gene coexpression network analysis was applied to construct gene network and classify genes into different modules. The most related module to high grade prostate cancer was identified and hub genes in the module were revealed. Ingenuity pathway analysis was applied to check the chosen module’s relationship to high grade prostate cancer. Hub gene’s expression profile was verified with clinical samples and a dataset from The Cancer Genome Atlas project.

Result

3193 differentially expressed genes were filtered and gene ontology and pathway analysis revealed some cancer- and sex hormone-related results. Weighted gene coexpression network was constructed and genes were classified into six modules. The red module was selected and ingenuity pathway analysis confirmed its relationship with high grade prostate cancer. Hub genes were identified and their expression profile was also confirmed.

Conclusion

The present study applied integrate bioinformatics approaches to generate a holistic view of high grade prostate cancer and identified hub genes could serve as prognosis markers and potential treatment targets.

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Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. Nat Genet 25:25–29. doi:10.1038/75556 CrossRefPubMedPubMedCentral

Assinder SJ, Dong Q, Kovacevic Z, Richardson DR (2009) The TGF-β, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer. Biochem J 417:411–421. doi:10.1042/BJ20081610 CrossRefPubMed

Barabasi A-L (2009) Scale-free networks: a decade and beyond. Science (80-) 325:412–413. doi:10.1126/science.1173299 CrossRef

Bi D, Ning H, Liu S et al (2015) Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer. Comput Biol Chem 56:71–83. doi:10.1016/j.compbiolchem.2015.04.001 CrossRefPubMed

Bibikova M, Chudin E, Arsanjani A et al (2007) Expression signatures that correlated with Gleason score and relapse in prostate cancer. Genomics 89:666–672. doi:10.1016/j.ygeno.2007.02.005 CrossRefPubMed

Bindea G, Mlecnik B, Hackl H et al (2009) ClueGO: a cytoscape plug-into decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091–1093. doi:10.1093/bioinformatics/btp101 CrossRefPubMedPubMedCentral

Blake JA, Christie KR, Dolan ME et al (2015) Gene ontology consortium: going forward. Nucleic Acids Res 43:D1049–D1056. doi:10.1093/nar/gku1179 CrossRef

Castilla C, Flores ML, Medina R et al (2014) Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin PTTG1. Mol Cancer Ther 13(10):2372–2383. doi:10.1158/1535-7163.MCT-13-0405 CrossRefPubMed

Cerami E, Gao J, Dogrusoz U et al (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404. doi:10.1158/2159-8290.CD-12-0095 CrossRefPubMed

Chen Z, Zhang C, Wu D et al (2011) Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth. EMBO J 30:2405–2419. doi:10.1038/emboj.2011.154 CrossRefPubMedPubMedCentral

Chiang YT, Wang K, Fazli L et al (2014) GATA2 as a potential metastasis-driving gene in prostate cancer. Oncotarget 5:451–461CrossRefPubMedPubMedCentral

Choi J-W, Kim Y, Lee J-H, Kim Y-S (2013) High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer. Virchows Arch 463:681–687. doi:10.1007/s00428-013-1473-6 CrossRefPubMed

Cui W, Qian Y, Zhou X et al (2015) Discovery and characterization of long intergenic non-coding RNAs (lincRNA) module biomarkers in prostate cancer: an integrative analysis of RNA-Seq data. BMC Genomics 16:S3. doi:10.1186/1471-2164-16-S7-S3 CrossRefPubMedPubMedCentral

Cuzick J, Swanson GP, Fisher G et al (2011) Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol 12:245–255. doi:10.1016/S1470-2045(10)70295-3 CrossRefPubMedPubMedCentral

de Resende MF, Vieira S, Chinen LT et al (2013) Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer. J Transl Med 11:36CrossRefPubMedPubMedCentral

Erho N, Crisan A, Vergara IA et al (2013) Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One 8:e66855. doi:10.1371/journal.pone.0066855 CrossRefPubMedPubMedCentral

Gao J, Aksoy BA, Dogrusoz U et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6:pl1. doi:10.1126/scisignal.2004088 CrossRefPubMedPubMedCentral

Ghazalpour A, Doss S, Zhang B et al (2006) Integrating genetic and network analysis to characterize genes related to mouse weight. PLoS Genet 2:1182–1192. doi:10.1371/journal.pgen.0020130 CrossRef

Gleason DF (1966) Classification of prostatic carcinomas. Cancer Chemother Rep 50:125–128PubMed

Gleason DF, Mellinger GT (1974) Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111:58–64CrossRefPubMed

Huang DW, Lempicki RA, Sherman BT (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. doi:10.1038/nprot.2008.211 CrossRef

Huang S, Liao Q, Li L, Xin D (2014) PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation. Tumour Biol 35:6265–6270CrossRefPubMed

Kanehisa M, Furumichi M, Tanabe M et al (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45:D353–D361. doi:10.1093/nar/gkw1092 CrossRefPubMed

Khatri P, Sirota M, Butte AJ (2012) Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol. doi:10.1371/journal.pcbi.1002375 PubMedPubMedCentral

Khongkow P, Gomes AR, Gong C et al (2016) Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance. Oncogene 35:990–1002. doi:10.1038/onc.2015.152 CrossRefPubMed

Kidokoro T, Tanikawa C, Furukawa Y et al (2008) CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene 27:1562–1571. doi:10.1038/sj.onc.1210799 CrossRefPubMed

Kim Y, Choi J-W, Lee J-H, Kim Y-S (2014) MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol 33:517–523. doi:10.1097/PGP.0000000000000082 CrossRefPubMed

Kirk JS, Schaarschuch K, Dalimov Z et al (2015) Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer. Oncotarget 6:3136–3146CrossRefPubMed

Kuner R, Fälth M, Pressinotti NC et al (2013) The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer. J Mol Med 91:237–248. doi:10.1007/s00109-012-0949-1 CrossRefPubMed

Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinform 9:559. doi:10.1186/1471-2105-9-559 CrossRef

Langfelder P, Zhang B, Horvath S (2008) Defining clusters from a hierarchical cluster tree: the dynamic tree cut package for R. Bioinformatics 24:719–720. doi:10.1093/bioinformatics/btm563 CrossRefPubMed

Lee B, Mazar J, Aftab MN et al (2014) Long noncoding RNAs as putative biomarkers for prostate cancer detection. J Mol Diagn 16:615–626. doi:10.1016/j.jmoldx.2014.06.009 CrossRefPubMedPubMedCentral

Li K, Mao Y, Lu L et al (2016) Silencing of CDC20 suppresses metastatic castration-resistant prostate cancer growth and enhances chemosensitivity to docetaxel. Int J Oncol 49:1679–1685. doi:10.3892/ijo.2016.3671 PubMed

Loeb S, Bruinsma SM, Nicholson J et al (2015) Active surveillance for prostate cancer: a systematic review of clinicopathologic variables and biomarkers for risk stratification. Eur Urol 67:619–626. doi:10.1016/j.eururo.2014.10.010 CrossRefPubMed

Ma R, Kang X, Zhang G et al (2016) High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma. Oncol Lett 11:2300–2304. doi:10.3892/ol.2016.4171 PubMedPubMedCentral

MacLennan NK, Dong J, Aten JE et al (2009) Weighted gene co-expression network analysis identifies biomarkers in glycerol kinase deficient mice. Mol Genet Metab 98:203–214. doi:10.1016/j.ymgme.2009.05.004 CrossRefPubMed

Malki K, Tosto MG, Jumabhoy I et al (2013) Integrative mouse and human mRNA studies using WGCNA nominates novel candidate genes involved in the pathogenesis of major depressive disorder research article. Pharmacogenomics 14:1979–1990. doi:10.2217/pgs.13.154 CrossRefPubMed

Mao Y, Li K, Lu L et al (2016) Overexpression of Cdc20 in clinically localized prostate cancer: relation to high Gleason score and biochemical recurrence after laparoscopic radical prostatectomy. Cancer Biomark 16:351–358CrossRefPubMed

Mason MJ, Fan G, Plath K et al (2009) Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells. BMC Genom 10:327. doi:10.1186/1471-2164-10-327 CrossRef

Moura IMB, Delgado ML, Silva PMA et al (2014) High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma. J Oral Pathol Med 43:225–231. doi:10.1111/jop.12115 CrossRefPubMed

Murphy AJ, Hughes CA, Barrett C et al (2007) Low-level TOP2A amplification in prostate cancer is associated with HER2 duplication, androgen resistance, and decreased survival. Cancer Res 67:2893–2898CrossRefPubMed

Psyrri A, Kalogeras KT, Kronenwett R et al (2012) Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study. Ann Oncol 23:1422–1427. doi:10.1093/annonc/mdr527 CrossRefPubMed

Puniya BL, Kulshreshtha D, Verma SP et al (2013) Integrated gene co-expression network analysis in the growth phase of Mycobacterium tuberculosis reveals new potential drug targets. Mol BioSyst 9:2798–2815. doi:10.1039/c3mb70278b CrossRefPubMed

R Core Team (2017) R: a language and environment for statistical computing

Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. doi:10.1101/gr.1239303 CrossRefPubMedPubMedCentral

Shen Z, Jiang X, Zeng C et al (2013) High expression of ubiquitin-conjugating enzyme 2C (UBE2C) correlates with nasopharyngeal carcinoma progression. BMC Cancer 13:192. doi:10.1186/1471-2407-13-192 CrossRefPubMedPubMedCentral

Shuliang S, Lei C, Guangwu J, Changjie L (2013) Involvement of ubiquitin-conjugating enzyme E2C in proliferation and invasion of prostate carcinoma cells. Oncol Res 21:121–127. doi:10.3727/096504013X13832473329953 CrossRefPubMed

Siegel RL, Miller KD, Jemal A (2016) Cancer statistics. CA Cancer J Clin 66:7–30. doi:10.3322/caac.21332 CrossRefPubMed

Stangel D, Erkan M, Buchholz M et al (2015) Kif20a inhibition reduces migration and invasion of pancreatic cancer cells. J Surg Res 197:91–100. doi:10.1016/j.jss.2015.03.070 CrossRefPubMed

Stark JR, Perner S, Stampfer MJ et al (2009) Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J Clin Oncol 27:3459–3464. doi:10.1200/JCO.2008.20.4669 CrossRefPubMedPubMedCentral

Taniuchi K, Furihata M, Saibara T (2014) KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells. Neoplasia 16:1082–1093. doi:10.1016/j.neo.2014.10.007 CrossRefPubMedPubMedCentral

Wan X, Huang W, Yang S et al (2016) Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer. Oncotarget 7:60503–60518. doi:10.18632/oncotarget.11391 CrossRefPubMedPubMedCentral

Wang Q, Li W, Zhang Y et al (2009) Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell 138:245–256. doi:10.1016/j.cell.2009.04.056 CrossRefPubMedPubMedCentral

Wang H, Zhang C, Rorick A et al (2011) CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability. Cancer Res 71:4866–4876. doi:10.1158/0008-5472.CAN-10-4576 CrossRefPubMedPubMedCentral

Wang L, Gong Y, Chippada-Venkata U et al (2015) A robust blood gene expression-based prognostic model for castration-resistant prostate cancer. BMC Med 13:201CrossRefPubMedPubMedCentral

Yan G-R, Zou F-Y, Dang B-L et al (2012) Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study. Proteomics 12:2391–2399. doi:10.1002/pmic.201100652 CrossRefPubMed

Zhang S, Cao J (2009) A close examination of double filtering with fold change and T test in microarray analysis. BMC Bioinform 10:402. doi:10.1186/1471-2105-10-402 CrossRef

Zhang B, Genetics H, Zhang B, Horvath S (2005) A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. doi:10.2202/1544-6115.1128 PubMed

Zhang W, He W, Shi Y et al (2016) High expression of KIF20A is associated with poor overall survival and tumor progression in early-stage cervical squamous cell carcinoma. PLoS One 11:e0167449. doi:10.1371/journal.pone.0167449 CrossRefPubMedPubMedCentral

Zhao S, Geybels MS, Leonardson A et al (2016) Epigenome-wide tumor DNA methylation profiling identifies novel prognostic biomarkers of metastatic-lethal progression in men with clinically localized prostate cancer. Clin Cancer Res. doi:10.1158/1078-0432.CCR-16-0549

Zhu X, Mao Z, Na Y et al (2006) Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer. Anticancer Res 26:1253–1259PubMed

Title: Identification of prognostic markers of high grade prostate cancer through an integrated bioinformatics approach
Authors: Hai Huang
Qin Zhang
Chen Ye
Jian-Min Lv
Xi Liu
Lu Chen
Hao Wu
Lei Yin
Xin-Gang Cui
Dan-Feng Xu
Wen-Hui Liu
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 12/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2497-0

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