Meta-analysis of Gene Expression Data Identifies Causal Genes for Prostate Cancer

  • Wang, Xiang-Yang (Department of Urology, Henan Provincial People's Hospital) ;
  • Hao, Jian-Wei (Department of Urology, Henan Provincial People's Hospital) ;
  • Zhou, Rui-Jin (Department of Urology, Henan Provincial People's Hospital) ;
  • Zhang, Xiang-Sheng (Department of Urology, Henan Provincial People's Hospital) ;
  • Yan, Tian-Zhong (Department of Urology, Henan Provincial People's Hospital) ;
  • Ding, De-Gang (Department of Urology, Henan Provincial People's Hospital) ;
  • Shan, Lei (Department of Urology, Henan Provincial People's Hospital)
  • Published : 2013.01.31


Prostate cancer is a leading cause of death in male populations across the globe. With the advent of gene expression arrays, many microarray studies have been conducted in prostate cancer, but the results have varied across different studies. To better understand the genetic and biologic mechanisms of prostate cancer, we conducted a meta-analysis of two studies on prostate cancer. Eight key genes were identified to be differentially expressed with progression. After gene co-expression analysis based on data from the GEO database, we obtained a co-expressed gene list which included 725 genes. Gene Ontology analysis revealed that these genes are involved in actin filament-based processes, locomotion and cell morphogenesis. Further analysis of the gene list should provide important clues for developing new prognostic markers and therapeutic targets.


  1. Stangelberger A, Waldert M, Djavan B (2008). Prostate cancer in elderly men. Rev Urol, 10, 111.
  2. Tuxhorn JA, Ayala GE, Rowley DR (2001). Reactive stroma in prostate cancer progression. J Urol, 166, 2472-83.
  3. Hudson RS, Yi M, Esposito D, et al (2012). MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer. Nucleic Acids Res, 40, 3689-703 .
  4. Jiang WG, Puntis MC, Hallett MB (1994). Molecular and cellular basis of cancer invasion and metastasis: implications for treatment. Br J Surg, 81, 1576-90.
  5. Jing L, Liu L, Yu YP, et al (2004). Expression of myopodin induces suppression of tumor growth and metastasis. Am J Pathol, 164, 1799-806.
  6. Kanehisa M (2002). The KEGG database. Novartis Found Symp, 247, 91-101; discussion -3, 19-28, 244-52.
  7. Korkola JE, Houldsworth J, Feldman DR, et al (2009). Identification and validation of a gene expression signature that predicts outcome in adult men with germ cell tumors. J Clin Oncol, 27, 5240-7.
  8. Liu R, Zhou Z, Huang J, Chen C (2011). PMEPA1 promotes androgen receptor-negative prostate cell proliferation through suppressing the Smad3/4-c-Myc-p21 Cip1 signaling pathway. J Pathol, 223, 683-94.
  9. Logothetis CJ, Lin SH (2005). Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer, 5, 21-8.
  10. Love HD, Booton SE, Boone BE, et al (2009). Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer. PLoS One, 4, e8384.
  11. Maere S, Heymans K, Kuiper M (2005). BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics, 21, 3448-9.
  12. Mathivanan S, Periaswamy B, Gandhi T, et al (2006). An evaluation of human protein-protein interaction data in the public domain. BMC Bioinformatics, 7, S19.
  13. McCabe CD, Spyropoulos DD, Martin D, Moreno CS (2008). Genome-wide analysis of the homeobox C6 transcriptional network in prostate cancer. Cancer Res, 68, 1988-96.
  14. Rhea JM, Singh HV, Molinaro RJ (2011). Next generation sequencing in the clinical molecular diagnosis of cancer. Medical Laboratory Observer.
  15. Rochester MA, Riedemann J, Hellawell GO, et al (2004). Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer. Cancer Gene Ther, 12, 90-100.
  16. Savinainen KJ, Saramaki OR, Linja MJ, et al (2002). Expression and gene copy number analysis of ERBB2 oncogene in prostate cancer. Am J Pathol, 160, 339.
  17. Shannon P, Markiel A, Ozier O, et al (2003). Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 13, 2498-504.
  18. Shen MM, Abate-Shen C (2010). Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev, 24, 1967-2000.
  19. Alberti C (2006). Prostate cancer progression and surrounding microenvironment. Int J Biol Markers, 21, 88-95.
  20. Astin JW, Batson J, Kadir S, et al (2010). Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells. Nat Cell Biol, 12, 1194-204.
  21. Berger MF, Lawrence MS, Demichelis F, et al (2011). The genomic complexity of primary human prostate cancer. Nature, 470, 214-20.
  22. Bonkhoff H (1998). Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status. Prostate Suppl, 8, 18-22.
  23. Boormans J, Korsten H, Ziel-van Der Made A, et al (2010). E17K substitution in AKT1 in prostate cancer. Bri J cancer, 102, 1491-4.
  24. Bubendorf L, Schopfer A, Wagner U, et al (2000). Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol, 31, 578-83.
  25. Chandran U, Ma C, Dhir R, et al (2007). Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer, 7, 64.
  26. Chen T, Yi SH, Liu XY, Liu ZG (2012). Meta-analysis of Associations between the MDM2-T309G polymorphism and prostate cancer risk. Asian Pac J Cancer Prev, 13, 4327-30.
  27. Chung LW, Baseman A, Assikis V, Zhau HE (2005). Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. J Urol, 173, 10-20.
  28. Cornet AM, Hanon E, Reiter ER, et al (2003). Prostatic androgen repressed message-1 (PARM-1) may play a role in prostatic cell immortalisation. Prostate, 56, 220-30.
  29. Dakhova O, Ozen M, Creighton CJ, et al (2009). Global gene expression analysis of reactive stroma in prostate cancer. Clin Cancer Res, 15, 3979-89.
  30. Fladeby C, Gupta SN, Barois N, et al (2008). Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells. Int J Cancer, 122, 1229-35.
  31. Fujita A, Gomes LR, Sato JR, et al (2008). Multivariate gene expression analysis reveals functional connectivity changes between normal/tumoral prostates. BMC Syst Biol, 2, 106.
  32. Glinsky GV, Glinskii AB, Stephenson AJ, et al (2004). Gene expression profiling predicts clinical outcome of prostate cancer. J Clini Invetst, 113, 913-23.
  33. Gorlov I, Byun J, Gorlova O, et al (2009). Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data. BMC Med Genomics, 2, 48.
  34. Guo YJ, Shi ZM, Liu JD, et al (2012). Meta-analysis of the relation between the VDR gene TaqIpolymorphism and genetic susceptibility to prostate cancer in Asian populations. Asian Pac J Cancer Prev, 13, 4441-4.
  35. Harris M, Clark J, Ireland A, et al (2004). The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res, 32, D258.

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