Investigation of the molecular mechanisms underlying postoperative recurrence in prostate cancer by gene expression profiling

Yajun,Cheng; Yuan,Tang; Zhong,Wang; Bin,Xu

doi:10.3892/etm.2017.5510

Investigation of the molecular mechanisms underlying postoperative recurrence in prostate cancer by gene expression profiling

Authors:
- Cheng Yajun
- Tang Yuan
- Wang Zhong
- Xu Bin
View Affiliations

Affiliations: Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China, Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
Published online on: November 14, 2017 https://doi.org/10.3892/etm.2017.5510
Pages: 761-768
Copyright : © Yajun et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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

The present study aimed to identify potential genes associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP) in order to improve the prediction of the prognosis of patients with PCa. The GSE25136 microarray dataset, including 39 recurrent and 40 non‑recurrent PCa samples, was downloaded from the Gene Expression Omnibus database. Differentially‑expressed genes (DEGs) were identified using limma packages, and the pheatmap package was used to present the DEGs screened using a hierarchical cluster analysis. Furthermore, gene ontology functional enrichment analysis was used to predict the potential functions of the DEGs. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to analyze pathway enrichment of DEGs in the regulatory network. Lastly, a protein‑protein interaction (PPI) network of the DEGs was constructed using Cytoscape software to understand the interactions between these DEGs. A total of 708 DEGs were identified in the recurrent and non‑recurrent PCa samples. Functional annotation revealed that these DEGs were primarily involved in cell adhesion, negative regulation of growth, and the cyclic adenosine monophosphate and mitogen‑activated protein kinase (MAPK) signaling pathways. Furthermore, five key genes, including cluster of differentiation 22, insulin‑like growth factor‑1, inhibin β A subunit, MAPK kinase 5 and receptor tyrosine kinase like orphan receptor 1, were identified through PPI network analysis. The results of the present study have provided novel ideas for predicting the prognosis of patients with PCa following RP.

View Figures

View References

1	Hu BR, Fairey AS, Madhav A, Yang D, Li M, Groshen S, Stephens C, Kim PH, Virk N, Wang L, et al: AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth. Prostate. 76:597–608. 2016. View Article : Google Scholar : PubMed/NCBI
2	Li HY, Jin N, Han YP and Jin XF: Pathway crosstalk analysis in prostate cancer based on protein-protein network data. Neoplasma. 64:22–31. 2017. View Article : Google Scholar : PubMed/NCBI
3	Stephenson AJ, Scardino PT, Eastham JA, Bianco FJ Jr, Dotan ZA, DiBlasio CJ, Reuther A, Klein EA and Kattan MW: Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol. 23:7005–7012. 2005. View Article : Google Scholar : PubMed/NCBI
4	Hu BR, Fairey AS, Madhav A, Yang D, Li M, Groshen S, Stephens C, Kim PH, Virk N, Wang L, et al: AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth. Prostate. 76:597–608. 2016. View Article : Google Scholar : PubMed/NCBI
5	Hao J, Chiang YT, Gout PW and Wang Y: Elevated XPO6 expression as a potential prognostic biomarker for prostate cancer recurrence. Front Biosci (Schol Ed). 8:44–55. 2016. View Article : Google Scholar : PubMed/NCBI
6	Choudhury AD, Eeles R, Freedland SJ, Isaacs WB, Pomerantz MM, Schalken JA, Tammela TL and Visakorpi T: The role of genetic markers in the management of prostate cancer. Eur Urol. 62:577–587. 2012. View Article : Google Scholar : PubMed/NCBI
7	Heidegger I, Höfer J, Luger M, Pichler R, Klocker H, Horninger W, Steiner E, Jochberger S and Culig Z: Is Eotaxin-1 a serum and urinary biomarker for prostate cancer detection and recurrence? Prostate. 75:1904–1909. 2015. View Article : Google Scholar : PubMed/NCBI
8	Stephenson AJ, Smith A, Kattan MW, Satagopan J, Reuter VE, Scardino PT and Gerald WL: Integration of gene expression profiling and clinical variables to predict prostate carcinoma recurrence after radical prostatectomy. Cancer. 104:290–298. 2005. View Article : Google Scholar : PubMed/NCBI
9	Sun Y and Goodison S: Optimizing molecular signatures for predicting prostate cancer recurrence. Prostate. 69:1119–1127. 2009. View Article : Google Scholar : PubMed/NCBI
10	Gene Ontology Consortium, . The Gene Ontology (GO) project in 2006. Nucleic Acids Res. 34(Database issue): D322–D326. 2006.PubMed/NCBI
11	Kanehisa M and Goto S.: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar : PubMed/NCBI
12	Thoma C: Prostate cancer: The genomics of localized disease. Nat Rev Urol. 14:652017. View Article : Google Scholar : PubMed/NCBI
13	Khor LY, Bae K, Al-Saleem T, Hammond EH, Grignon DJ, Sause WT, Pilepich MV, Okunieff PP, Sandler HM and Pollack A: Protein kinase A RI-alpha predicts for prostate cancer outcome: analysis of radiation therapy oncology group trial 86–10. Int J Radiat Oncol Biol Phys. 71:1309–1315. 2008. View Article : Google Scholar : PubMed/NCBI
14	Govindan R: The Washington Manual of Oncology. 2nd. Lippincott Williams and Wilkins; Philadelphia: 2008
15	Merkle D and Hoffmann R: Roles of cAMP and cAMP-dependent protein kinase in the progression of prostate cancer: Cross-talk with the androgen receptor. Cell Signal. 23:507–515. 2011. View Article : Google Scholar : PubMed/NCBI
16	Rahrmann EP, Collier LS, Knutson TP, Doyal ME, Kuslak SL, Green LE, Malinowski RL, Roethe L, Akagi K, Waknitz M, et al: Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen. Cancer Res. 69:4388–4397. 2009. View Article : Google Scholar : PubMed/NCBI
17	Henderson DJ, Byrne A, Dulla K, Jenster G, Hoffmann R, Baillie GS and Houslay MD: The cAMP phosphodiesterase-4D7 (PDE4D7) is downregulated in androgen-independent prostate cancer cells and mediates proliferation by compartmentalising cAMP at the plasma membrane of VCaP prostate cancer cells. Br J Cancer. 110:1278–1287. 2014. View Article : Google Scholar : PubMed/NCBI
18	Böttcher R, Henderson DJ, Dulla K, van Strijp D, Waanders LF, Tevz G, Lehman ML, Merkle D, van Leenders GJ, Baillie GS, et al: Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG-positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression. Br J Cancer. 113:1502–1511. 2015. View Article : Google Scholar : PubMed/NCBI
19	Böttcher R, Dulla K, van Strijp D, Dits N, Verhoef EI, Baillie GS, van Leenders GJ, Houslay MD, Jenster G and Hoffmann R: Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases. Oncotarget. 7:70669–70684. 2016.PubMed/NCBI
20	Koul HK, Pal M and Koul S: Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer. 4:342–359. 2013. View Article : Google Scholar : PubMed/NCBI
21	Guan M, Fousek K and Chow WA: Nelfinavir inhibits regulated intramembrane proteolysis of sterol regulatory element binding protein-1 and activating transcription factor 6 in castration-resistant prostate cancer. FEBS J. 279:2399–2411. 2012. View Article : Google Scholar : PubMed/NCBI
22	Bach LA and Hale LJ: Insulin-like growth factors and kidney disease. Am J Kidney Dis. 65:327–336. 2015. View Article : Google Scholar : PubMed/NCBI
23	Shanmugalingam T, Bosco C, Ridley AJ and Van Hemelrijck M: Is there a role for IGF-1 in the development of second primary cancers? Cancer Med. 5:3353–3367. 2016. View Article : Google Scholar : PubMed/NCBI
24	Cao Y, Nimptsch K, Shui IM, Platz EA, Wu K, Pollak MN, Kenfield SA, Stampfer MJ and Giovannucci EL: Prediagnostic plasma IGFBP-1, IGF-1 and risk of prostate cancer. Int J Cancer. 136:2418–2426. 2015. View Article : Google Scholar : PubMed/NCBI
25	Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R and Barrett JC: Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res. 57:4667–4672. 1997.PubMed/NCBI
26	McKeown BT and Hurta RA: Magnolol affects expression of IGF-1 and associated binding proteins in human prostate cancer cells in vitro. Anticancer Res. 34:6333–6338. 2014.PubMed/NCBI
27	Shukla S, MacLennan GT, Fu P and Gupta S: Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous mouse prostate cancer model. Pharm Res. 29:1506–2617. 2012. View Article : Google Scholar : PubMed/NCBI
28	Tsuchiya N, Narita S, Inoue T, Saito M, Numakura K, Huang M, Hatakeyama S, Satoh S, Saito S, Ohyama C, et al: Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis. BMC Cancer. 13:1502013. View Article : Google Scholar : PubMed/NCBI
29	Mehta PB, Jenkins BL, McCarthy L, Thilak L, Robson CN, Neal DE and Leung HY: MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion. Oncogene. 22:1381–1389. 2003. View Article : Google Scholar : PubMed/NCBI
30	Ma W, He X, Zhang H, Liu T, Feng X and Zhou Q: Down-regulation of receptor-tyrosine-kinase-like orphan receptor 1 suppresses cell growth and enhances apoptosis in human colorectal carcinoma. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 32:655–665. 2016.(In Chinese). PubMed/NCBI
31	Hojjat-Farsangi M, Moshfegh A, Daneshmanesh AH, Khan AS, Mikaelsson E, Osterborg A and Mellstedt H: The receptor tyrosine kinase ROR1-an oncofetal antigen for targeted cancer therapy. Semin Cancer Biol. 29:21–31. 2014. View Article : Google Scholar : PubMed/NCBI
32	Oshima T, Yoshihara K, Aoyama T, Hasegawa S, Sato T, Yamamoto N, Akito N, Shiozawa M, Yoshikawa T, Numata K, et al: Relation of INHBA gene expression to outcomes in gastric cancer after curative surgery. Anticancer Res. 34:2303–2309. 2014.PubMed/NCBI
33	Lee HY, Li CC, Huang CN, Li WM, Yeh HC, Ke HL, Yang KF, Liang PI, Li CF and Wu WJ: INHBA overexpression indicates poor prognosis in urothelial carcinoma of urinary bladder and upper tract. J Surg Oncol. 111:414–422. 2015. View Article : Google Scholar : PubMed/NCBI
34	Okano M, Yamamoto H, Ohkuma H, Kano Y, Kim H, Nishikawa S, Konno M, Kawamoto K, Haraguchi N, Takemasa I, et al: Significance of INHBA expression in human colorectal cancer. Oncol Rep. 30:2903–2908. 2013. View Article : Google Scholar : PubMed/NCBI
35	Tuscano JM, Kato J, Pearson D, Xiong C, Newell L, Ma Y, Gandara DR and O'Donnell RT: CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy. Cancer Res. 72:5556–5565. 2012. View Article : Google Scholar : PubMed/NCBI
36	Pop LM, Barman S, Shao C, Poe JC, Venturi GM, Shelton JM, Pop IV, Gerber DE, Girard L, Liu XY, et al: A reevaluation of CD22 expression in human lung cancer. Cancer Res. 74:263–271. 2014. View Article : Google Scholar : PubMed/NCBI