Combinations of elevated tissue miRNA‑17‑92 cluster expression and serum prostate‑specific antigen as potential diagnostic biomarkers for prostate cancer

Feng,Sujuan; Qian,Xiaosong; Li,Han; Zhang,Xiaodong

doi:10.3892/ol.2017.7026

Combinations of elevated tissue miRNA‑17‑92 cluster expression and serum prostate‑specific antigen as potential diagnostic biomarkers for prostate cancer

Authors:
- Sujuan Feng
- Xiaosong Qian
- Han Li
- Xiaodong Zhang
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Affiliations: Institute of Uro‑Nephrology, Nephrology Faculty, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China, Department of Blood Purification, Nephrology Faculty, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China
Published online on: September 22, 2017 https://doi.org/10.3892/ol.2017.7026
Pages: 6943-6949

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Abstract

The aim of the present study was to investigate the effectiveness of the miR‑17‑92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)‑17‑92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate‑specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR‑17‑92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan‑Meier analysis was plotted to investigate the predictive potential of miR‑17‑92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR‑17‑92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR‑17‑92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR‑17‑92 cluster was associated with shorter biochemical recurrence interval. miR‑17‑92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR‑17‑92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

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1	Torre LA, Siegel RL, Ward EM and Jemal A: Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Biomarkers Prev. 25:16–27. 2016. View Article : Google Scholar : PubMed/NCBI
2	Saad F and Fizazi K: Androgen deprivation therapy and secondary hormone therapy in the management of hormone-sensitive and castration resistant prostate cancer. Urology. 86:852–861. 2015. View Article : Google Scholar : PubMed/NCBI
3	Ren SC, Chen R and Sun YH: Prostate cancer research in China. Asian J Androl. 15:350–353. 2013. View Article : Google Scholar : PubMed/NCBI
4	Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, et al: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 360:1320–1328. 2009. View Article : Google Scholar : PubMed/NCBI
5	Carthew RW and Sontheimer EJ: Origins and Mechanisms of miRNAs and siRNAs. Cell. 136:642–655. 2009. View Article : Google Scholar : PubMed/NCBI
6	Vanacore D, Boccellino M, Rossetti S, Cavaliere C, D'Aniello C, Di Franco R, Romano FJ, Montanari M, La Mantia E, Piscitelli R, et al: Micrornas in prostate cancer: An overview. Oncotarget. 2017.[Epub ahead of print]. View Article : Google Scholar
7	Fuziwara CS and Kimura ET: Insights into regulation of the miR-17-92 cluster of miRNAs in cancer. Front Med (Lausanne). 2:642015.PubMed/NCBI
8	Olive V, Li Q and He L: mir-17-92: A polycistronic oncomir with pleiotropic functions. Immunol Rev. 253:158–166. 2013. View Article : Google Scholar : PubMed/NCBI
9	Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y and Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65:9628–9632. 2005. View Article : Google Scholar : PubMed/NCBI
10	He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ and Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI
11	Arabi L, Gsponer JR, Smida J, Nathrath M, Perrina V, Jundt G, Ruiz C, Quagliata L and Baumhoer D: Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma-reasons and consequences. Genes Cancer. 5:56–63. 2014.PubMed/NCBI
12	John-Aryankalayil M, Palayoor ST, Makinde AY, Cerna D, Simone CB II, Falduto MT, Magnuson SR and Coleman CN: Fractionated radiation alters oncomir and tumor suppressor miRNAs in human prostate cancer cells. Radiat Res. 178:105–117. 2012. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Rees MA, Resnick MI and Oesterling JE: Use of prostate-specific antigen, Gleason score and digital rectal examination in staging patients with newly diagnosed prostate cancer. Urol Clin North Am. 24:379–388. 1997. View Article : Google Scholar : PubMed/NCBI
15	Catto JW, Alcaraz A, Bjartell AS, De Vere White R, Evans CP, Fussel S, Hamdy FC, Kallioniemi O, Mengual L, Schlomm T and Visakorpi T: MicroRNA in prostate, bladder and kidney cancer: A systematic review. Eur Urol. 59:671–681. 2011. View Article : Google Scholar : PubMed/NCBI
16	Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL and Visakorpi T: MicroRNA expression profiling in prostate cancer. Cancer Res. 67:6130–6135. 2007. View Article : Google Scholar : PubMed/NCBI
17	Lichner Z, Fendler A, Saleh C, Nasser AN, Boles D, Al-Haddad S, Kupchak P, Dharsee M, Nuin PS, Evans KR, et al: MicroRNA signature helps distinguish early from late biochemical failure in prostate cancer. Clin Chem. 59:1595–1603. 2013. View Article : Google Scholar : PubMed/NCBI
18	Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y and Seto M: Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 64:3087–3095. 2004. View Article : Google Scholar : PubMed/NCBI
19	Mendell JT: miRiad roles for the miR-17-92 cluster in development and disease. Cell. 133:217–222. 2008. View Article : Google Scholar : PubMed/NCBI
20	Mogilyansky E and Rigoutsos I: The miR-17/92 cluster: A comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 20:1603–1614. 2013. View Article : Google Scholar : PubMed/NCBI
21	Zhu H, Han C and Wu T: MiR-17-92 cluster promotes hepatocarcinogenesis. Carcinogenesis. 36:1213–1222. 2015. View Article : Google Scholar : PubMed/NCBI
22	Go H, Jang JY, Kim PJ, Kim YG, Nam SJ, Paik JH, Kim TM, Heo DS, Kim CW and Jeon YK: MicroRNA-21 plays an oncogenic role by targeting FOXO1 and activating the PI3K/AKT pathway in diffuse large B-cell lymphoma. Oncotarget. 6:15035–15049. 2015. View Article : Google Scholar : PubMed/NCBI
23	Saki N, Abroun S, Soleimani M, Hajizamani S, Shahjahani M, Kast RE and Mortazavi Y: Involvement of microRNA in T-cell differentiation and malignancy. Int J Hematol Oncol Stem Cell Res. 9:33–49. 2015.PubMed/NCBI
24	Osada H and Takahashi T: let-7 and miR-17-92: Small-sized major players in lung cancer development. Cancer Sci. 102:9–17. 2011. View Article : Google Scholar : PubMed/NCBI
25	Jin L, Lim M, Zhao S, Sano Y, Simone BA, Savage JE, Wickstrom E, Camphausen K, Pestell RG and Simone NL: The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster. Breast Cancer Res Treat. 146:41–50. 2014. View Article : Google Scholar : PubMed/NCBI
26	Servín-González LS, Granados-López AJ and López JA: Families of microRNAs expressed in clusters regulate cell signaling in cervical cancer. Int J Mol Sci. 16:12773–12790. 2015. View Article : Google Scholar : PubMed/NCBI
27	Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, Ferbeyre G and Chartrand P: An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 282:2135–2143. 2007. View Article : Google Scholar : PubMed/NCBI
28	Pasqualini L, Bu H, Puhr M, Narisu N, Rainer J, Schlick B, Schäfer G, Angelova M, Trajanoski Z, Börno ST, et al: miR-22 and miR-29a are members of the androgen receptor cistrome modulating LAMC1 and Mcl-1 in prostate cancer. Mol Endocrinol. 29:1037–1054. 2015. View Article : Google Scholar : PubMed/NCBI
29	Yang X, Du WW, Li H, Liu F, Khorshidi A, Rutnam ZJ and Yang BB: Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res. 41:9688–9704. 2013. View Article : Google Scholar : PubMed/NCBI
30	Wang SY, Shiboski S, Belair CD, Cooperberg MR, Simko JP, Stoppler H, Cowan J, Carroll PR and Blelloch R: miR-19, miR-345, miR-519c-5p serum levels predict adverse pathology in prostate cancer patients eligible for active surveillance. PLoS One. 9:e985972014. View Article : Google Scholar : PubMed/NCBI
31	Pesta M, Klecka J, Kulda V, Topolcan O, Hora M, Eret V, Ludvikova M, Babjuk M, Novak K, Stolz J and Holubec L: Importance of miR-20a expression in prostate cancer tissue. Anticancer Res. 30:3579–3583. 2010.PubMed/NCBI
32	Komatsu S, Ichikawa D, Takeshita H, Morimura R, Hirajima S, Tsujiura M, Kawaguchi T, Miyamae M, Nagata H, Konishi H, et al: Circulating miR-18a: A sensitive cancer screening biomarker in human cancer. In Vivo. 28:293–297. 2014.PubMed/NCBI
33	Shen Z, Wu X, Wang Z, Li B and Zhu X: Effect of miR-18a overexpression on the radiosensitivity of non-small cell lung cancer. Int J Clin Exp Pathol. 8:643–648. 2015.PubMed/NCBI
34	Su ZX, Zhao J, Rong ZH, Wu YG, Geng WM and Qin CK: Diagnostic and prognostic value of circulating miR-18a in the plasma of patients with gastric cancer. Tumour Biol. 35:12119–12125. 2014. View Article : Google Scholar : PubMed/NCBI
35	Li T, Li RS, Li YH, Zhong S, Chen YY, Zhang CM, Hu MM and Shen ZJ: miR-21 as an independent biochemical recurrence predictor and potential therapeutic target for prostate cancer. J Urol. 187:1466–1472. 2012. View Article : Google Scholar : PubMed/NCBI
36	Kobayashi N, Uemura H, Nagahama K, Okudela K, Furuya M, Ino Y, Ito Y, Hirano H, Inayama Y, Aoki I, et al: Identification of miR-30d as a novel prognostic maker of prostate cancer. Oncotarget. 3:1455–1471. 2012. View Article : Google Scholar : PubMed/NCBI
37	Barron N, Keenan J, Gammell P, Martinez VG, Freeman A, Masters JR and Clynes M: Biochemical relapse following radical prostatectomy and miR-200a levels in prostate cancer. Prostate. 72:1193–1199. 2012. View Article : Google Scholar : PubMed/NCBI
38	Goto Y, Kojima S, Nishikawa R, Enokida H, Chiyomaru T, Kinoshita T, Nakagawa M, Naya Y, Ichikawa T and Seki N: The microRNA-23b/27b/24-1 cluster is a disease progression marker and tumor suppressor in prostate cancer. Oncotarget. 5:7748–7759. 2014. View Article : Google Scholar : PubMed/NCBI