Skip to main content
Top
Published in: Diagnostic Pathology 1/2014

Open Access 01-12-2014 | Research

RETRACTED ARTICLE: Dysregulation of cell cycle related genes and microRNAs distinguish the low- from high-risk of prostate cancer

Authors: Jiling Wen, Rongbing Li, Xiaofei Wen, Guangming Chou, Jiasun Lu, Xuelei Wang, Yongchao Jin

Published in: Diagnostic Pathology | Issue 1/2014

Login to get access

Abstract

Background

Prostate cancer (PCa) is a biologically heterogeneous disease with considerable variation in clinical aggressiveness. In this study, bioinformatics was used to detect the patterns of gene expression alterations of PCa patients.

Methods

The gene expression profile GSE21034 and GSE21036 were downloaded from Gene Expression Omnibus (GEO) database. Significantly changed mRNA transcripts and microRNAs were identified between subtypes with favorable (cluster 2) and unfavorable (cluster 5) prognosis by two-side unequal variances t test. MicroRNAs and their potential target genes were identified by TargetScan and miRTarBase, respectively. Besides, the overlapped genes between the target genes of microRNAs and mRNA transcripts were assessed by Fisher’ exact test (one side). The functional annotation was performed by DAVID, followed by construction of protein-protein interaction (PPI) network.

Results

Compared to cluster 2, 1556 up-regulated and 1288 down-regulated transcripts were identified in cluster 5. Total 28 microRNAs were up-regulated and 30 microRNAs were down-regulated in cluster 5. Besides, 12 microRNAs target transcripts were significantly overlapped with down-regulated transcripts in cluster 5 with none of them was found overlapped with up-regulated transcripts. Functional annotation showed that cell cycle was the most significant function. In the PPI network, BRCA1, CDK1, TK1 and TRAF2 were hub protein of signature genes in cluster 5, and TGFBR1, SMAD2 and SMAD4 were hub proteins of signature gnens in cluster 2.

Conclusions

Our findings raise the possibility that genes related with cell cycle and dysregulated miRNA at diagnosis might have clinical utility in distinguishing low- from high-risk PCa patients.

Virtual slides

Appendix
Available only for authorised users
Literature
1.
go back to reference Chan JM, Jou RM, Carroll PR: The relative impact and future burden of prostate cancer in the United States. J Urol. 2004, 172: S13-S16. 10.1097/01.ju.0000142068.66876.53. discussion S17PubMedCrossRef Chan JM, Jou RM, Carroll PR: The relative impact and future burden of prostate cancer in the United States. J Urol. 2004, 172: S13-S16. 10.1097/01.ju.0000142068.66876.53. discussion S17PubMedCrossRef
2.
go back to reference Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62: 10-29. 10.3322/caac.20138.PubMedCrossRef Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62: 10-29. 10.3322/caac.20138.PubMedCrossRef
3.
4.
go back to reference Berezikov E, Guryev V, Van De Belt J, Wienholds E, Plasterk RH, Cuppen E: Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005, 120: 21-24. 10.1016/j.cell.2004.12.031.PubMedCrossRef Berezikov E, Guryev V, Van De Belt J, Wienholds E, Plasterk RH, Cuppen E: Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005, 120: 21-24. 10.1016/j.cell.2004.12.031.PubMedCrossRef
5.
go back to reference Logothetis CJ, Lin SH: Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer. 2005, 5: 21-28. 10.1038/nrc1528.PubMedCrossRef Logothetis CJ, Lin SH: Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer. 2005, 5: 21-28. 10.1038/nrc1528.PubMedCrossRef
6.
go back to reference Nogueira L, Corradi R, Eastham JA: Other biomarkers for detecting prostate cancer. BJU Int. 2010, 105: 166-169. 10.1111/j.1464-410X.2009.09088.x.PubMedCrossRef Nogueira L, Corradi R, Eastham JA: Other biomarkers for detecting prostate cancer. BJU Int. 2010, 105: 166-169. 10.1111/j.1464-410X.2009.09088.x.PubMedCrossRef
7.
go back to reference Hoque MO, Kim MS, Ostrow KL, Liu J, Wisman GB, Park HL, Poeta ML, Jeronimo C, Henrique R, Lendvai A, Schuuring E, Begum S, Rosenbaum E, Ongenaert M, Yamashita K, Califano J, Westra W, Van Der Zee AG, Van Criekinge W, Sidransky D: Genome-wide promoter analysis uncovers portions of the cancer methylome. Cancer Res. 2008, 68: 2661-2670. 10.1158/0008-5472.CAN-07-5913.PubMedPubMedCentralCrossRef Hoque MO, Kim MS, Ostrow KL, Liu J, Wisman GB, Park HL, Poeta ML, Jeronimo C, Henrique R, Lendvai A, Schuuring E, Begum S, Rosenbaum E, Ongenaert M, Yamashita K, Califano J, Westra W, Van Der Zee AG, Van Criekinge W, Sidransky D: Genome-wide promoter analysis uncovers portions of the cancer methylome. Cancer Res. 2008, 68: 2661-2670. 10.1158/0008-5472.CAN-07-5913.PubMedPubMedCentralCrossRef
8.
go back to reference Schilling D, De Reijke T, Tombal B, De La Taille A, Hennenlotter J, Stenzl A: The Prostate Cancer gene 3 assay: indications for use in clinical practice. BJU Int. 2010, 105: 452-455. 10.1111/j.1464-410X.2009.09085.x.PubMedCrossRef Schilling D, De Reijke T, Tombal B, De La Taille A, Hennenlotter J, Stenzl A: The Prostate Cancer gene 3 assay: indications for use in clinical practice. BJU Int. 2010, 105: 452-455. 10.1111/j.1464-410X.2009.09085.x.PubMedCrossRef
9.
go back to reference Hoque MO: DNA methylation changes in prostate cancer: current developments and future clinical implementation. Expert Rev Mol Diagn. 2009, 9: 243-257. 10.1586/erm.09.10.PubMedPubMedCentralCrossRef Hoque MO: DNA methylation changes in prostate cancer: current developments and future clinical implementation. Expert Rev Mol Diagn. 2009, 9: 243-257. 10.1586/erm.09.10.PubMedPubMedCentralCrossRef
10.
go back to reference Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL: Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010, 18: 11-22. 10.1016/j.ccr.2010.05.026.PubMedPubMedCentralCrossRef Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL: Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010, 18: 11-22. 10.1016/j.ccr.2010.05.026.PubMedPubMedCentralCrossRef
11.
12.
go back to reference Friedman RC, Farh KK, Burge CB, Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009, 19: 92-105. 10.1101/gr.082701.108.PubMedPubMedCentralCrossRef Friedman RC, Farh KK, Burge CB, Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009, 19: 92-105. 10.1101/gr.082701.108.PubMedPubMedCentralCrossRef
13.
go back to reference Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, Tsai WT, Chen GZ, Lee CJ, Chiu CM, Chien CH, Wu MC, Huang CY, Tsou AP, Huang HD: miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res. 2011, 39: D163-D169. 10.1093/nar/gkq1107.PubMedPubMedCentralCrossRef Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, Tsai WT, Chen GZ, Lee CJ, Chiu CM, Chien CH, Wu MC, Huang CY, Tsou AP, Huang HD: miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res. 2011, 39: D163-D169. 10.1093/nar/gkq1107.PubMedPubMedCentralCrossRef
14.
go back to reference Daya S: Fisher exact test. Evid Based Obstet Gynecol. 2002, 4: 3-4. 10.1054/ebog.2002.0026.CrossRef Daya S: Fisher exact test. Evid Based Obstet Gynecol. 2002, 4: 3-4. 10.1054/ebog.2002.0026.CrossRef
15.
go back to reference Das J, Yu H: HINT: high-quality protein interactomes and their applications in understanding human disease. BMC Syst Biol. 2012, 6: 92-10.1186/1752-0509-6-92.PubMedPubMedCentralCrossRef Das J, Yu H: HINT: high-quality protein interactomes and their applications in understanding human disease. BMC Syst Biol. 2012, 6: 92-10.1186/1752-0509-6-92.PubMedPubMedCentralCrossRef
16.
go back to reference Xu K, Wu ZJ, Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, Xu H, Cato L, Thornton JE, Gregory RI, Morrissey C, Vessella RL, Montironi R, Magi-Galluzzi C, Kantoff PW, Balk SP, Liu XS, Brown M: EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science. 2012, 338: 1465-1469. 10.1126/science.1227604.PubMedPubMedCentralCrossRef Xu K, Wu ZJ, Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, Xu H, Cato L, Thornton JE, Gregory RI, Morrissey C, Vessella RL, Montironi R, Magi-Galluzzi C, Kantoff PW, Balk SP, Liu XS, Brown M: EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science. 2012, 338: 1465-1469. 10.1126/science.1227604.PubMedPubMedCentralCrossRef
17.
go back to reference Whitfield ML, Sherlock G, Saldanha AJ, Murray JI, Ball CA, Alexander KE, Matese JC, Perou CM, Hurt MM, Brown PO, Botstein D: Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell. 2002, 13: 1977-2000. 10.1091/mbc.02-02-0030..PubMedPubMedCentralCrossRef Whitfield ML, Sherlock G, Saldanha AJ, Murray JI, Ball CA, Alexander KE, Matese JC, Perou CM, Hurt MM, Brown PO, Botstein D: Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell. 2002, 13: 1977-2000. 10.1091/mbc.02-02-0030..PubMedPubMedCentralCrossRef
18.
go back to reference Mandal RK, Mittal RD: Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population?. Urol Oncol. 2010, 30: 555-561. 10.1016/j.urolonc.2010.05.006.PubMedCrossRef Mandal RK, Mittal RD: Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population?. Urol Oncol. 2010, 30: 555-561. 10.1016/j.urolonc.2010.05.006.PubMedCrossRef
19.
go back to reference Cuzick J, Swanson GP, Fisher G, Brothman AR, Berney DM, Reid JE, Mesher D, Speights VO, Stankiewicz E, Foster CS, Moller H, Scardino P, Warren JD, Park J, Younus A, Flake DD, Wagner S, Gutin A, Lanchbury JS, Stone S: Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol. 2011, 12: 245-255. 10.1016/S1470-2045(10)70295-3.PubMedPubMedCentralCrossRef Cuzick J, Swanson GP, Fisher G, Brothman AR, Berney DM, Reid JE, Mesher D, Speights VO, Stankiewicz E, Foster CS, Moller H, Scardino P, Warren JD, Park J, Younus A, Flake DD, Wagner S, Gutin A, Lanchbury JS, Stone S: Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol. 2011, 12: 245-255. 10.1016/S1470-2045(10)70295-3.PubMedPubMedCentralCrossRef
20.
go back to reference Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, Fuse M, Ichikawa T, Naya Y, Nakagawa M, Seki N: Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012, 106: 405-413. 10.1038/bjc.2011.462.PubMedPubMedCentralCrossRef Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, Fuse M, Ichikawa T, Naya Y, Nakagawa M, Seki N: Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012, 106: 405-413. 10.1038/bjc.2011.462.PubMedPubMedCentralCrossRef
21.
go back to reference Sun X, Liu Z, Yang Z, Xiao L, Wang F, He Y, Su P, Wang J, Jing B: Association of microRNA-126 expression with clinicopathological features and the risk of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy. Diagn Pathol. 2013, 8: 1746-1596. 10.1186/1746-1596-8-208.CrossRef Sun X, Liu Z, Yang Z, Xiao L, Wang F, He Y, Su P, Wang J, Jing B: Association of microRNA-126 expression with clinicopathological features and the risk of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy. Diagn Pathol. 2013, 8: 1746-1596. 10.1186/1746-1596-8-208.CrossRef
22.
go back to reference Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, Yee AJ, Ang LC, He C, Shan SW, Yang BB: MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene. 2011, 30: 806-821. 10.1038/onc.2010.465.PubMedCrossRef Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, Yee AJ, Ang LC, He C, Shan SW, Yang BB: MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene. 2011, 30: 806-821. 10.1038/onc.2010.465.PubMedCrossRef
23.
go back to reference Li Y, Tan W, Neo TW, Aung MO, Wasser S, Lim SG, Tan TM: Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Sci. 2009, 100: 1234-1242. 10.1111/j.1349-7006.2009.01164.x.PubMedCrossRef Li Y, Tan W, Neo TW, Aung MO, Wasser S, Lim SG, Tan TM: Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Sci. 2009, 100: 1234-1242. 10.1111/j.1349-7006.2009.01164.x.PubMedCrossRef
24.
go back to reference Yang IP, Tsai HL, Hou MF, Chen KC, Tsai PC, Huang SW, Chou WW, Wang JY, Juo SH: MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle. Carcinogenesis. 2012, 33: 1522-1530. 10.1093/carcin/bgs166.PubMedCrossRef Yang IP, Tsai HL, Hou MF, Chen KC, Tsai PC, Huang SW, Chou WW, Wang JY, Juo SH: MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle. Carcinogenesis. 2012, 33: 1522-1530. 10.1093/carcin/bgs166.PubMedCrossRef
25.
go back to reference Tian Y, Zhao L, Zhang H, Liu X, Zhao X, Li Y, Li J: AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression. Diagn Pathol. 2014, 9: 1746-1596. Tian Y, Zhao L, Zhang H, Liu X, Zhao X, Li Y, Li J: AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression. Diagn Pathol. 2014, 9: 1746-1596.
26.
go back to reference Heinlein CA, Chang C: Androgen receptor in prostate cancer. Endocr Rev. 2004, 25: 276-308. 10.1210/er.2002-0032.PubMedCrossRef Heinlein CA, Chang C: Androgen receptor in prostate cancer. Endocr Rev. 2004, 25: 276-308. 10.1210/er.2002-0032.PubMedCrossRef
27.
go back to reference Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA: Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor. Cancer Res. 2000, 60: 5946-5949.PubMed Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA: Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor. Cancer Res. 2000, 60: 5946-5949.PubMed
28.
go back to reference Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C: Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells. Proc Natl Acad Sci U S A. 2000, 97: 11256-11261. 10.1073/pnas.190353897.PubMedPubMedCentralCrossRef Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C: Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells. Proc Natl Acad Sci U S A. 2000, 97: 11256-11261. 10.1073/pnas.190353897.PubMedPubMedCentralCrossRef
29.
go back to reference Chen S, Xu Y, Yuan X, Bubley GJ, Balk SP: Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1. Proc Natl Acad Sci U S A. 2006, 103: 15969-15974. 10.1073/pnas.0604193103.PubMedPubMedCentralCrossRef Chen S, Xu Y, Yuan X, Bubley GJ, Balk SP: Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1. Proc Natl Acad Sci U S A. 2006, 103: 15969-15974. 10.1073/pnas.0604193103.PubMedPubMedCentralCrossRef
Metadata
Title
RETRACTED ARTICLE: Dysregulation of cell cycle related genes and microRNAs distinguish the low- from high-risk of prostate cancer
Authors
Jiling Wen
Rongbing Li
Xiaofei Wen
Guangming Chou
Jiasun Lu
Xuelei Wang
Yongchao Jin
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2014
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-014-0156-1

Other articles of this Issue 1/2014

Diagnostic Pathology 1/2014 Go to the issue