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

Guoliang Zheng,Yan Zhao,Zhichao Zheng,Guojun Zhang

doi:10.3389/fonc.2021.560136

Guoliang Zheng, Yan Zhao + Show 2 more

Open Access

https://doi.org/10.3389/fonc.2021.560136

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Abstract

We constructed a prognostic risk model for colon adenocarcinoma (COAD) using microRNAs (miRNAs) as biomarkers. Clinical data of patients with COADs and miRNA-seq data were from TCGA, and the differential expression of miRNAs (carcinoma vs. para-carcinoma tissues) was assessed using R software. COAD data were randomly divided into Training and Testing Sets. A linear prognostic risk model was constructed using Cox regression analysis based on the Training Set. Patients were classified as high-risk or low-risk according to the score of the prognostic model. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate model performance. The gene targets in the prognostic model were identified and their biological functions were analyzed. Analysis of COAD and normal cell lines using qPCR was used to verify the model. There were 134 up-regulated and 140 down-regulated miRNAs. We used the Training Set to develop a prognostic model based on the expression of seven miRNAs. ROC analysis indicated this model had acceptable prediction accuracy (area under the curve=0.784). Kaplan-Meier survival analysis showed that overall survival was worse in the high-risk group. Cox regression analysis showed that the 7-miRNA Risk Score was an independent prognostic factor. The 2,863 predicted target genes were mainly enriched in the MAPK, PI3K-AKT, proteoglycans in cancer, and mTOR signaling pathways. For unknown reasons, expression of these miRNAs in cancerous and normal cells differed somewhat from model predictions. Regardless, the 7-miRNA Risk Score can be used to predict COAD prognosis and may help to guide clinical treatment.

Highlights

Colon cancer is among the most common malignancies worldwide and is associated with high morbidity and mortality [1]
The general goals of this study were to determine the relationships of different miRNAs with Colon adenocarcinoma (COAD), and to identify specific miRNAs that may be used as biomarkers to supplement the traditional histopathological prognostic factors and improve the individualized treatment of COAD patients
We examined miRNA data from 380 COAD tissues and eight adjacent normal tissues and clinical data from 385 patients with COADs to develop a prognostic risk model (Figure 1)

Summary

Introduction

Colon cancer is among the most common malignancies worldwide and is associated with high morbidity and mortality [1]. Colon adenocarcinoma (COAD) is the most common type of colon cancer. The potential clinical strategies for treatment of COAD include surgery, chemotherapy, radiotherapy, and targeted therapies. Because of the incomplete understanding of the Prognostic miRNA Biomarkers of COAD pathogenesis of COAD, there are no targeted treatments currently used in clinical practice. Chemotherapy regimens are generally is limited by poor drug bioavailability, multidrug resistance, and high toxicity, and these can lead to significant adverse effects and reduce treatment efficacy [2]. Further studies of the pathogenesis and progression of COAD are needed so that new treatments can be developed

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