Serum-Based MicroRNA Signature Predicts Relapse and Therapeutic Outcome of Adjuvant Chemotherapy in Colorectal Cancer Patients

Background: Approximately 60% of patients with colorectal cancer (CRC) undergo either local recurrence or distant metastases after surgery. Current prognostic biomarkers are insufficient to predict recurrence of CRC and provide little forecast information about what patients are likely to receive benefit from the adjuvant chemotherapy. As microRNAs (miRNAs) constantly exist in human serum and being used to predict the prognosis of a various cancers, this study was designed to identify miRNA-based circulating biomarkers to predict clinical outcomes of CRC. Methods: A serum-focused miRNA expression was used to investigate if miRNA expression profiles could predict the clinical outcomes of patients with CRC. We created miRNA signature profiles associated in the training set (n = 40), and further validated its prediction in two independent testing cohorts. Results: Using Cox regression and risk-score analysis, we identified a four-miRNA signature (miR-652, miR-342, miR-501, and miR-328) for the prediction of tumor relapse and the overall survival(OS) of patients with CRC in the training set (n = 40). This miRNA signature was further validated in a testing set (n = 226) and another independent cohort (n = 56). A high-risk signature score was significantly associated with CRC tumor recurrence and poor treatment outcome. Multivariable Cox regression models indicated that the risk score, based on the four-miRNA signature, was an independent prognostic classifier for patients with CRC. Conclusions: The serum miRNA signature may serve as a minimally invasive predictor for tumor relapse and treatment outcome in patients with CRC and provide a useful reference for treatment selection. Funding Statement: This work was supported by the National Natural Science Foundation of China (81372593, 81201965, 81772565), Beijing Natural Science Foundation (7132052), and the National High Technology Research and Development Program of China (863 Program) (No.2012AA02A506, 2014AA020801). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This research was approved by the ethics committee of the Health Science Center of Peking University and the Oncology Center at Peking University and Zhejiang University. Written informed consent was obtained from all participants before enrollment to the study.