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PLOS ONE  2013 

Differentially Expressed Androgen-Regulated Genes in Androgen-Sensitive Tissues Reveal Potential Biomarkers of Early Prostate Cancer

DOI: 10.1371/journal.pone.0066278

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Abstract:

Background Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer. Methods ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan? low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1). Results and Discussion By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94). Conclusions We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools.

References

[1]  Gronberg H (2003) Prostate cancer epidemiology. Lancet 361: 859–864.
[2]  Catalona WJ, Smith DS, Ratliff TL, Basler JW (1993) Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. Jama 270: 948–954.
[3]  Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, et al. (1999) DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 59: 5975–5979.
[4]  Sorensen KD, Orntoft TF (2010) Discovery of prostate cancer biomarkers by microarray gene expression profiling. Expert Rev Mol Diagn 10: 49–64.
[5]  Bradford TJ, Tomlins SA, Wang X, Chinnaiyan AM (2006) Molecular markers of prostate cancer. Urol Oncol 24: 538–551.
[6]  Rittenhouse H, Blase A, Shamel B, Schalken J, Groskopf J (2013) The long and winding road to FDA approval of a novel prostate cancer test: our story. Clin Chem 59: 32–34.
[7]  Culig Z (2003) Role of the androgen receptor axis in prostate cancer. Urology 62: 21–26.
[8]  Heinlein CA, Chang C (2004) Androgen receptor in prostate cancer. Endocr Rev 25: 276–308.
[9]  Han G, Buchanan G, Ittmann M, Harris JM, Yu X, et al. (2005) Mutation of the androgen receptor causes oncogenic transformation of the prostate. Proc Natl Acad Sci U S A 102: 1151–1156.
[10]  Torring N, Dagnaes-Hansen F, Sorensen BS, Nexo E, Hynes NE (2003) ErbB1 and prostate cancer: ErbB1 activity is essential for androgen-induced proliferation and protection from the apoptotic effects of LY294002. Prostate 56: 142–149.
[11]  Wang YZ, Wong YC (1998) Sex hormone-induced prostatic carcinogenesis in the noble rat: the role of insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the development of prostate cancer. Prostate 35: 165–177.
[12]  Stanbrough M, Leav I, Kwan PW, Bubley GJ, Balk SP (2001) Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium. Proc Natl Acad Sci U S A 98: 10823–10828.
[13]  Mani RS, Tomlins SA, Callahan K, Ghosh A, Nyati MK, et al. (2009) Induced chromosomal proximity and gene fusions in prostate cancer. Science 326: 1230.
[14]  Altintas DM, Vlaeminck V, Angelov D, Dimitrov S, Samarut J (2011) Cell cycle regulated expression of NCoR might control cyclic expression of androgen responsive genes in an immortalized prostate cell line. Mol Cell Endocrinol 332: 149–162.
[15]  Goulter AB, Harmer DW, Clark KL (2006) Evaluation of low density array technology for quantitative parallel measurement of multiple genes in human tissue. BMC Genomics 7: 34.
[16]  Rhim JS, Webber MM, Bello D, Lee MS, Arnstein P, et al. (1994) Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras. Proc Natl Acad Sci U S A 91: 11874–11878.
[17]  Bello D, Webber MM, Kleinman HK, Wartinger DD, Rhim JS (1997) Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. Carcinogenesis 18: 1215–1223.
[18]  Windus LC, Kiss DL, Glover T, Avery VM (2012) In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer. Exp Cell Res 318: 2507–2519.
[19]  Webber MM, Bello D, Kleinman HK, Hoffman MP (1997) Acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells. Carcinogenesis 18: 1225–1231.
[20]  Reissigl A, Pointner J, Strasser H, Ennemoser O, Klocker H, et al. (1997) Frequency and clinical significance of transition zone cancer in prostate cancer screening. Prostate 30: 130–135.
[21]  Landers KA, Burger MJ, Tebay MA, Purdie DM, Scells B, et al. (2005) Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int J Cancer 114: 950–956.
[22]  Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, et al. (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44: 8–15.
[23]  Balcerczak E, Mirowski M, Sasor A, Wierzbicki R (2003) Expression of p65, DD3 and c-erbB2 genes in prostate cancer. Neoplasma 50: 97–101.
[24]  Klecka J, Holubec L, Pesta M, Topolcan O, Hora M, et al. (2010) Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis. Anticancer Res 30: 665–670.
[25]  Bialkowska-Hobrzanska H, Driman DK, Fletcher R, Harry V, Razvi H (2006) Expression of human telomerase reverse transcriptase, Survivin, DD3 and PCGEM1 messenger RNA in archival prostate carcinoma tissue. Can J Urol 13: 2967–2974.
[26]  Floriano-Sanchez E, Cardenas-Rodriguez N, Castro-Marin M, Alvarez-Grave P, Lara-Padilla E (2009) DD3(PCA3) gene expression in cancer and prostatic hyperplasia. Clin Invest Med 32: E258.
[27]  Vlaeminck-Guillem V, Ruffion A, Andre J, Devonec M, Paparel P (2010) Urinary prostate cancer 3 test: toward the age of reason? Urology 75: 447–453.
[28]  Auprich M, Bjartell A, Chun FK, de la Taille A, Freedland SJ, et al. (2011) Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur Urol 60: 1045–1054.
[29]  de Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, et al. (2002) DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 62: 2695–2698.
[30]  Vest D, Schalken JA, Muir G, Dasgupta P (2010) Transmembrane protease serine 2 in prostate cancer. BJU Int 105: 1490–1492.
[31]  Pascal LE, Vencio RZ, Page LS, Liebeskind ES, Shadle CP, et al. (2009) Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes. BMC Cancer 9: 452.
[32]  Merlo GR, Zerega B, Paleari L, Trombino S, Mantero S, et al. (2000) Multiple functions of Dlx genes. Int J Dev Biol 44: 619–626.
[33]  Huggett J, Dheda K, Bustin S, Zumla A (2005) Real-time RT-PCR normalisation; strategies and considerations. Genes Immun 6: 279–284.
[34]  Matsumoto A, Arai Y, Urano A, Hyodo S (1992) Effect of androgen on the expression of gap junction and beta-actin mRNAs in adult rat motoneurons. Neurosci Res 14: 133–144.
[35]  Matsumoto A, Arai Y, Urano A, Hyodo S (1994) Androgen regulates gene expression of cytoskeletal proteins in adult rat motoneurons. Horm Behav 28: 357–366.
[36]  Ohl F, Jung M, Xu C, Stephan C, Rabien A, et al. (2005) Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization? J Mol Med 83: 1014–1024.
[37]  Lin H, Juang JL, Wang PS (2004) Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis. J Biol Chem 279: 29302–29307.
[38]  Kristiansen G, Pilarsky C, Wissmann C, Stephan C, Weissbach L, et al. (2003) ALCAM/CD166 is up-regulated in low-grade prostate cancer and progressively lost in high-grade lesions. Prostate 54: 34–43.
[39]  Vare P, Loikkanen I, Hirvikoski P, Vaarala MH, Soini Y (2008) Low claudin expression is associated with high Gleason grade in prostate adenocarcinoma. Oncol Rep 19: 25–31.
[40]  Doane AS, Danso M, Lal P, Donaton M, Zhang L, et al. (2006) An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25: 3994–4008.
[41]  Ferreira LB, Palumbo A, de Mello KD, Sternberg C, Caetano MS, et al. (2012) PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling. BMC Cancer 12: 507.
[42]  Thompson M, Lapointe J, Choi YL, Ong DE, Higgins JP, et al. (2008) Identification of candidate prostate cancer genes through comparative expression-profiling of seminal vesicle. Prostate 68: 1248–1256.
[43]  Arrigo AP, Simon S, Gibert B, Kretz-Remy C, Nivon M, et al. (2007) Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett 581: 3665–3674.
[44]  Li X, Jia Z, Shen Y, Ichikawa H, Jarvik J, et al. (2008) Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate. Cancer Sci 99: 1326–1333.
[45]  Vanaja DK, Ehrich M, Van den Boom D, Cheville JC, Karnes RJ, et al. (2009) Hypermethylation of genes for diagnosis and risk stratification of prostate cancer. Cancer Invest 27: 549–560.
[46]  DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44: 837–845.
[47]  O'Malley KJ, Dhir R, Nelson JB, Bost J, Lin Y, et al. (2009) The expression of androgen-responsive genes is up-regulated in the epithelia of benign prostatic hyperplasia. Prostate 69: 1716–1723.

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