Identification and Evaluation of Plasma MicroRNAs for Early Detection of Colorectal Cancer

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers. Circulating microRNAs (miRNAs) have been suggested as potentially promising markers for early detection of CRC. We aimed to identify and evaluate a panel of miRNAs that might be suitable for CRC early detection. Methods: MiRNAs were profiled by TaqMan MicroRNA Array and screened for differential expression in 5 pools of plasma samples of CRC patients (N = 50) and 5 pools of neoplasm-free controls (N = 50). Additional miRNAs were selected from a literature review. Identified candidates were evaluated in independent validation samples with respect to discrimination of CRC patients (N = 80) or advanced adenoma patients (N = 50) and neoplasm-free controls (N = 194). Diagnostic performance of the panel of miRNAs was assessed by multiple logistic regression, using bootstrap analysis to correct for over-optimism. Results: Five miRNAs identified to be differentially expressed from TaqMan MicroRNA Array (miR-29a, -106b, -133a, -342-3p, -532-3p), and seven miRNAs reported to be differentially expressed in the literature (miR-18a, -20a, -21, -92a, -143, -145, 181b) were selected for validation. Nine of the twelve miRNAs (miR-18a, -20a, -21, -29a, -92a, -106b, -133a, -143, -145) were found to be differentially expressed in CRC patients and controls in the validation samples. The optimism-corrected area under the curve was 0.745 (95% confidence interval: 0.708-0.846). None of the selected miRNAs showed significant differential expression between advanced adenoma patients and neoplasm-free controls. Conclusion: The identified panel of miRNAs could be of potential use in the development of a multi-marker blood based test for early detection of CRC. Impact: The study underscores the high potential of plasma miRNAs for the improvement of current offers of non-invasive CRC screening.