AUTHOR=Zheng Guoliang , Zhang GuoJun , Zhao Yan , Zheng Zhichao 

TITLE=Screening of miRNAs as Prognostic Biomarkers for Colon Adenocarcinoma and Biological Function Analysis of Their Target Genes

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.560136

DOI=10.3389/fonc.2021.560136

ISSN=2234-943X

ABSTRACT=Objective to construct a prognostic risk model of colon adenocarcinoma (COAD) based on Micro RNA (miRNA) to search for prognostic biomarkers. MiRNA-seq data and clinical data of COAD were downloaded from TCGA database, and the differential expression of miRNAs between carcinoma and para-carcinoma tissues was screened using R package. COAD data were randomly divided into training set and testing set by 1:1. Subsequently, a linear prognostic risk model of miRNA was constructed using Cox regression analysis based on training set data. Patients were divided into high-risk group and low-risk group according to the scores of the prognostic model, and K-M survival analysis and ROC curves were performed in the test group and the whole group respectively to evaluate the predictive power of the prognostic model. The target genes of miRNAs in the prognostic model were predicted and their biological functions were analyzed. Finally, qPCR was used to verify the reliability of differential expression of miRNAs in the model. A total of 274 differentially expressed miRNAs were screened (134 up-regulated, 140 down-regulated). Based on 173 cases in the training set, a prognostic model consisting of 7-miRNA (hsa-miR-194-3p, hsa-miR-21-3p, hsa-miR-193b-5p, hsa-miR-193a-5p, hsa-miR-3677-3p, hsa-miR-125b-5p, hsa-miR-3648) was constructed, with moderate prediction accuracy (AUC=0.784). Kaplan-Meier and Survival status charts showed that overall survival in the high-risk group was worse than that in the low-risk group. Univariate and multivariate COX analysis showed that 7-miRNA was an independent prognostic factor. A total of 2,863 target genes were predicted, mainly enriched in MAPK signaling pathway, PI3K-AKT signaling pathway, Proteoglycans in cancer signaling pathway, and mTOR signaling pathway. The results of qPCR verification of 7 miRNAs in the model were consistent with the results of differential expression analysis of TCGA data. The prognostic risk model of 7-miRNA can be used to predict the prognosis of COAD, which is conducive to further guiding clinical treatment.