Abstract

Abstract MicroRNAs (miRNAs) are associated with the development of nearly all cancers and serum miRNAs are promising biomarkers for early detection, diagnosis, and prognosis of cancer. We sought to identify serum miRNAs as potential diagnostic biomarkers for bladder cancer. To this end, global miRNA profiling was performed on sera in a pilot sample set containing matched non-muscle-invasive bladder cancer (NMIBC) and healthy controls to identify highly abundant serum miRNAs. Eighty nine miRNAs were stably detectable in cases and controls and selected for further testing. These 89 miRNAs were simultaneously quantified by high-throughput Taqman analysis using the Fluidigm BioMark™ HD System in a discovery set (140 NMIBC patients and 139 control subjects) and a validation set (140 NMIBC patients and 139 control subjects). In the discovery phase, 12 miRNAs showed significant differential expression between NMIBC patients and controls. In the validation phase, expression of one miRNA, miR-409-3p, remained significantly down-regulated in patients with NMIBC as compared to controls. The risk estimates of bladder cancer for miR-409-3p by tertile distributions in controls showed a significant trend for increased risk at the highest tertile for the whole sample set (odds ratio (OR) = 2.26; 95% confidence interval (CI) =1.42-3.59; P = 5.95 × 10−4) as well as for age > 65 (OR = 2.32; 95% CI =1.24-4.34; P =4.60 × 10−3) and ever smokers (OR = 2.34; 95% CI =1.31-4.18; P =4.05 × 10−3). Analyses of joint effects of this risk factor showed that the OR was statistically significantly elevated to 5.21 (95% CI =2.72-10.00; P =6.84 × 10−7) for the sample set including both the lowest level of miR-409-3p and ever smokers. Thus the differential expression miR-409-3p in serum distinguishes NMIBC and controls and may contribute to bladder cancer development. Citation Format: Jie Lian, Shu-Hong Lin, Sherri Luo, Maosheng Huang, Jian Gu, Ashish M. Kamat, Colin P. Dinney, Xifeng Wu. Serum microRNA profiling in non-muscle invasive bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5062. doi:10.1158/1538-7445.AM2014-5062

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