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Clinical and Translational Oncology

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01-10-2013 | Research Article

Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer

Authors: S. Wang, Q. Li, K. Wang, Y. Dai, J. Yang, S. Xue, F. Han, Q. Zhang, J. Liu, W. Wu

Published in: Clinical and Translational Oncology | Issue 10/2013

Abstract

Purpose

MicroRNA-31 (miR-31) has different expression patterns in various human cancers. Especially in urothelial carcinoma of the bladder, it has been demonstrated to be decreased expression in the invasive tumors and homozygously deleted. However, its clinical significance in human bladder cancer has not yet been elucidated. Thus, the purpose of this study was to investigate the diagnostic and prognostic values of miR-31 in this disease.

Methods

Expression levels of miR-31 in 126 pairs of bladder cancer and adjacent normal tissues were detected by real-time quantitative RT-PCR assay. To determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis.

Results

MiR-31 expression in bladder cancer tissues was significantly lower than those in adjacent normal tissues (mean expression level: 2.1 ± 0.9 vs. 3.8 ± 1.2, P < 0.001). When categorized into low vs. high expression, low miR-31 expression was negatively associated with the tumor stage (P = 0.02), the status of recurrence (P = 0.01), progression (P = 0.01), and death (P = 0.006) of patients with bladder cancer. Moreover, low miR-31 expression clearly predicted poorer PFS (P = 0.001) and OS (P < 0.001). In the multivariate analysis, low miR-31 expression was an independent prognostic factor for both PFS (P = 0.01) and OS (P = 0.008).

Conclusion

These findings show that miR-31 may contribute to the progression of bladder cancer and its downregulation may be independently associated with unfavorable PFS and OS, suggesting that miR-31 might be a promising marker for further risk stratification in the treatment of this cancer.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249PubMedCrossRef

Droller MJ (1998) Bladder cancer: state-of-the-art care. CA Cancer J Clin 48:269–284PubMedCrossRef

Vaishampayan U (2009) Systemic therapy of advanced urothelial cancer. Curr Treat Options Oncol 10:256–266PubMedCrossRef

Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19:666–675PubMed

Quek ML, Stein JP, Clark PE, Daneshmand S, Miranda G, Cai J et al (2003) Natural history of surgically treated bladder carcinoma with extravesical tumor extension. Cancer 98:955–961PubMedCrossRef

Khaled HM, Bahnassi AA, Zekri AR, Kassem HA, Mokhtar N (2003) Correlation between p53 mutations and HPV in bilharzial bladder cancer. Urol Oncol 21:334–341PubMedCrossRef

Dinney CP, McConkey DJ, Millikan RE (2004) Focus on bladder cancer. Cancer Cell 6:111–116PubMedCrossRef

Wang M, Chu H, Li P, Yuan L, Fu G, Ma L et al (2012) Genetic variants in microRNAs predict bladder cancer risk and recurrence. Cancer Res 72:6173–6182PubMedCrossRef

Williams MB, Liana A (2011) MicroRNAs in bladder cancer. In: Cho WCS (ed) MicroRNAs in cancer translational research. Springer, Netherlands, pp 223–237CrossRef

10.

Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM (2006) MicroRNA expression and function in cancer. Trends Mol Med 12:580–587PubMedCrossRef

11.

Catto JW, Alcaraz A, Bjartell AS, De Vere White R, Evans CP, Fussel S et al (2011) MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol 59:671–681PubMedCrossRef

12.

Song T, Xia W, Shao N, Zhang X, Wang C, Wu Y et al (2010) Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pac J Cancer Prev 11:905–911PubMed

13.

Valastyan S, Weinberg RA (2010) miR-31: a crucial overseer of tumor metastasis and other emerging roles. Cell Cycle 9:2124–2129PubMedCrossRef

14.

Wszolek MF, Rieger-Christ KM, Kenney PA, Gould JJ, Silva Neto B, Lavoie AK et al (2011) A MicroRNA expression profile defining the invasive bladder tumor phenotype. Urol Oncol 29:794–801. e1

15.

Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H et al (2009) MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 124:2236–2242PubMedCrossRef

16.

Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414PubMedCrossRef

17.

Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27:91–105PubMedCrossRef

18.

Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC et al (2009) A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137:1032–1046PubMedCrossRef

19.

Bandre’s E (2006) Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and nontumoral tissues. Mol Cancer 5:29

20.

Wang CJ, Zhou ZG, Wang L, Yang L, Zhou B, Gu J et al (2009) Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers 26:27–34PubMedCrossRef

21.

Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC (2010) Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis 16:360–364PubMedCrossRef

22.

Yan LX (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14:2348–2360PubMedCrossRef

23.

Zhang Y, Guo J, Li D, Xiao B, Miao Y, Jiang Z et al (2010) Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance. Med Oncol 27:685–689PubMedCrossRef

24.

Tan X, Qin W, Zhang L, Hang J, Li B, Zhang C et al (2011) A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin Cancer Res 17:6802–6811PubMedCrossRef

25.

Zhang T, Wang Q, Zhao D, Cui Y, Cao B, Guo L et al (2011) The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma. Clin Sci (Lond) 121:437–447CrossRef

26.

Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M et al (2010) The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle 9:4387–4398PubMedCrossRef

27.

Xu RS, Wu XD, Zhang SQ, Li CF, Yang L, Li DD et al (2013) The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer. Int J Oncol 42:676–682PubMed

28.

Asangani IA, Harms PW, Dodson L, Pandhi M, Kunju LP, Maher CA et al (2012) Genetic and epigenetic loss of microRNA-31 leads to feed-forward expression of EZH2 in melanoma. Oncotarget 3:1011–1025PubMed

29.

Chang KW, Kao SY, Wu YH, Tsai MM, Tu HF, Liu CJ et al (2013) Passenger strand miRNA miR-31(*) regulates the phenotypes of oral cancer cells by targeting RhoA. Oral Oncol 49:27–33PubMedCrossRef

Title: Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer
Authors: S. Wang
Q. Li
K. Wang
Y. Dai
J. Yang
S. Xue
F. Han
Q. Zhang
J. Liu
W. Wu
Publication date: 01-10-2013
Publisher: Springer Milan
Published in: Clinical and Translational Oncology / Issue 10/2013
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-013-1014-4

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