Serum microRNAs as predictors of risk for non-muscle invasive bladder cancer
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Jie Lian1, Shu-Hong Lin1, Yuanqing Ye1, David W. Chang1, Maosheng Huang1, Colin P. Dinney2 and Xifeng Wu1
1Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Xifeng Wu, email: [email protected]
Keywords: serum miRNA; biomarker; expression ratio; risk score; non-muscle-invasive bladder cancer
Abbreviations: NMIBC: non-muscle invasive bladder cancer; miRNA: microRNA
Received: May 24, 2017 Accepted: January 13, 2018 Epub: February 12, 2018 Published: March 13, 2018
MicroRNAs (miRNAs) are implicated in the development of nearly all cancers and may function as promising biomarkers for early detection, diagnosis and prognosis. We sought to investigate the role of serum miRNAs as potential diagnostic biomarkers or biomarkers of risk for early-stage bladder cancer. First, we profiled global serum miRNAs in a pilot set of 10 non-muscle invasive bladder cancer (NMIBC) cases and 10 healthy controls matched on age, gender and smoking status. Eighty nine stably detectable miRNAs were selected for further testing and quantification by high-throughput Taqman analysis using the Fluidigm BioMark HD System to assess their association with NMIBC risk in both discovery and validation sets totaling 280 cases and 278 controls. We found miR-409-3p and six miRNAs expression ratios were significantly associated with risk of bladder cancer in both discovery and validation sets. Interestingly, we identified expression of miR-409-3p and miR-342-3p inversely correlated with age and age of onset of NMIBC. A risk score was generated based on the combination of three miRNA ratios (miR-29a-3p/miR-222-3p, miR-150-5p/miR-331-3p, miR-409-3p/miR-423-5p). In dichotomized analysis, we found individuals with high risk score showed increased risk of bladder cancer in the discovery, validation, and combined sets. Pathway enrichment analyses suggested altered miRNAs and cognate target genes are linked to the retinoid acid receptor (RAR) signaling pathway. Overall, these results suggested specific serum miRNA signatures may serve as noninvasive predictors of NMIBC risk. Biological insights underlying bladder cancer development based on the pathway enrichment analysis may reveal novel therapeutic targets for personalized medicine.
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