A Novel Four-MicroRNA Signature for Prognosis and Diagnosis in Colorectal Cancer

Abstract

Background and aims: Colorectal cancer (CRC) remains a global public health problem. We aimed to access prognostic microRNAs (miRNAs) associated with overall survival (OS) and evaluate their diagnostic value in CRC.Methods: Three serum miRNA expression profiles from Gene Expression Omnibus (GEO) database and tissue miRNA expression profile of CRC from The Cancer Genome Atlas (TCGA) database were studied to get common differentially expressed miRNA (DEmiRNAs) in serums and tissues. 569 CRC patients with survival information from TCGA database were randomly divided into the discovery and validation cohort. Based on the TCGA discovery cohort, the univariate cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate cox proportional hazards regression analysis were performed and a prognostic signature was constructed. The prognostic capacity of the signature was verified in TCGA validation cohort and the prognostic signature expression in tumors and serums was validated in an independent microarray dataset and our clinical set. We also evaluated the diagnostic power of the model in serum by calculating the area under the receiver operating characteristic (ROC) curve in a clinical set. Functional enrichment analyses were applied to analyze the potential roles of the signature in CRC.Results: A total of 154 common DEmiRNAs were identified. Based on the TCGA discovery cohort, a four-miRNA (miR-10b, miR-130a, miR-561, miR-4684) prognostic signature was constructed and a predictive nomogram model including the expression of above four miRNAs showed good performance for predicting the 3- and 5-year overall survival. The findings were well verified in TCGA validation cohort. miR-10b, miR-130a, miR-561 and miR-4684 were significantly upregulated both in CRC tumors and serums. Circulating miR-10b, miR-130a, miR-561 and miR-4684 levels were significantly downregulated after surgical resection of tumor in CRC patients, suggesting these four circulating miRNAs in the serum were tumor derived. The four circulating miRNA combination might act as a novel diagnostic signature for CRC. Functional enrichment analyses suggested that above four miRNAs might be related to the progression of CRC. Conclusions: We developed a novel reliable prognostic and diagnostic signature, which should be beneficial for CRC screening and clinical therapeutic decision-making.