Abstract
BackgroundThe aim was to identify a novel prognostic miRNA signature for colon cancer (CC) in silico.MethodsData on the expression of miRNAs and relevant clinical information for 407 patients were obtained from The Cancer Genome Atlas (TCGA), and the samples were randomly split into a validation set (n = 203) and training set (n = 204). The differential expression of miRNAs between normal tissues and patients with CC was analyzed. We detected a miRNA expression signature in the training dataset by using a Cox proportional hazard regression model. Then, we verified the signature in the validation set. Association of the miRNA signature with overall survival was assessed in the validation cohort and combined cohort by log-rank test and based on Kaplan-Meier curves. The receiver operating characteristic and disease-free survival analyses were performed to evaluate the miRNA signature of CC in the combined cohort. Multivariate and univariate Cox analyses related to survival for the miRNA signature were performed, and a nomogram was built as a prognostic model for CC. To explore the function of target genes of the miRNA signature, Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used.ResultsBetween the matched normal tissues and colon cancer tissues, 267 differentially expressed miRNAs were detected, and a single-factor CoxPH model showed that 13 miRNAs were related to overall survival in the training cohort. Then, a five-miRNA signature was identified using a CoxPH regression model with multiple factors. The five-miRNA signature had significant prognostic value in the training cohort and was validated in the validation cohort and combined cohort. A total of 193 target genes of the miRNA signature were identified. According to the results of functional analysis of the target genes, the signaling pathways MAPK, AMPK and PI3K-Akt, focal adhesion, and microRNAs in cancer were remarkably enriched.ConclusionA five-miRNA signature had increased prognostic value for CC, which may provide important biological insights for the discovery and development of molecular predictors to improve the prognosis of patients with CC.
Highlights
Colon cancer (CC) is a common malignant tumor of the digestive tract worldwide
Between the matched normal tissues and colon cancer tissues, 267 differentially expressed miRNAs were detected, and a single-factor Cox proportional hazard (CoxPH) model showed that 13 miRNAs were related to overall survival in the training cohort
A five-miRNA signature had increased prognostic value for CC, which may provide important biological insights for the discovery and development of molecular predictors to improve the prognosis of patients with CC
Summary
Colon cancer (CC) is a common malignant tumor of the digestive tract worldwide. The incidence ranks third among all malignant tumors, and over 1 million new cases occur per year. [1] Despite continuous improvements in surgery, chemotherapy and radiotherapy, approximately 50% of patients still have recurrence and metastasis within 5 years, which leads to death.[2]. [1] Despite continuous improvements in surgery, chemotherapy and radiotherapy, approximately 50% of patients still have recurrence and metastasis within 5 years, which leads to death.[2] great progress has been made in understanding the pathogenesis and molecular mechanisms of CC, there is no effective molecular diagnostic approach to predict prognosis. Several miRNAs have been identified to predict prognosis in colon cancer, but there have been inconsistencies in previous studies. MiRNA expression signatures associated with prognosis have been identified in malignancy.[14] in our study, a novel miRNA signature capable of predicting prognosis in CC patients, was identified and validated in TCGA (The Cancer Genome Atlas) database. The aim was to identify a novel prognostic miRNA signature for colon cancer (CC) in silico. Editor: Rajeev Samant, University of Alabama at Birmingham, UNITED STATES
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