Systematic literature review and clinical validation of circulating microRNAs as diagnostic biomarkers for colorectal cancer
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Cheng Pan1,2,*, Xuebing Yan1,*, Hao Li1,*, Linsheng Huang1,*, Mingming Yin1, Yongzhi Yang1, Renyuan Gao1, Leiming Hong1,3, Yanlei Ma1, Chenzhang Shi1, Huanlong Qin1 and Peng Zhang1
1Department of General Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University No. 301, Shanghai 200072, China
2Medical Department, Soochow University, Jiangsu 215123, China
3Department of General Surgery, Weihai Municipal Hospital, Shandong 264200, China
*These authors have contributed equally to this work
Huanlong Qin, email: [email protected]
Peng Zhang, email: [email protected]
Keywords: colorectal cancer, circulating microRNAs, diagnosis, biomarkers
Received: November 30, 2016 Accepted: June 20, 2017 Published: July 18, 2017
Because patients with colorectal cancer (CRC) are usually diagnosed at an advanced stage and current serum tumor markers have limited diagnostic efficacy, there is an urgent need to identify reliable diagnostic biomarkers. To better define the diagnostic potential of microRNAs (miRNAs) for CRC, we performed a comprehensive evaluation of reported circulating CRC miRNA markers. After a systematic literature review, we selected 30 candidate miRNAs and used quantitative real-time polymerase chain reaction to examine their expression in a training cohort of 120 plasma samples (CRC vs healthy controls (HC) = 60:60). Expression data was confirmed in a validation cohort of 160 plasma samples (CRC vs HC = 80:80). We ultimately identified 5 dysregulated circulating miRNAs (miR-15b, miR-17, miR-21, miR-26b, and miR-145), of which miR-21 and miR-26b proved to have the best diagnostic performance in the training and validation cohorts, respectively. Based on these results, we propose a novel blood-based diagnostic model, integrating 5 CRC-related miRNAs and serum carcinoembryonic antigen (CEA), which provides better diagnostic performance than the combined 5 miRNAs, CEA alone, or any single miRNA. We propose that the novel CRC diagnostic model presented here will be useful for overcoming the limitations faced by current non-invasive diagnostic strategies.
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