Identification of key modules and micro RNAs associated with colorectal cancer via a weighted gene co-expression network analysis and competing endogenous RNA network analysis

J Gastrointest Oncol. 2023 Jun 30;14(3):1320-1330. doi: 10.21037/jgo-23-244. Epub 2023 Jun 21.

Abstract

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, and the incidence of CRC has increased rapidly in recent years. Due to the high invasiveness of colonoscopy and the low accuracy of alternative diagnostic methods, the diagnosis of CRC remains a serious problem. Thus, molecular biomarkers for CRC need to be identified.

Methods: In this study, RNA-sequencing data from The Cancer Genome Atlas (TCGA) database were used to identify the long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and micro RNAs (miRNAs) that were differentially expressed between the CRC and normal tissues. Based on the gene expression and clinical features, the results of the weighted gene co-expression network analysis (WGCNA) and the binding relationships between miRNAs and lncRNAs and mRNAs were used to establish a CRC-related competing endogenous RNA (ceRNA) network.

Results: The core miRNAs (i.e., mir-874, mir-92a-1, and mir-940) in the network were identified. Among them, mir-874 was negatively correlated with the overall survival (OS) of patients. The protein-coding genes in the ceRNA network included IZUMO4, WT1, NPEPL1, TEX22, PPFIA4, and SFXN3, and the lncRNAs were LINC00858 and PRR7-AS1. These genes were significantly highly expressed in CRC according to validations in other independent data sets.

Conclusions: In conclusion, this study established a network of the co-expressed ceRNAs associated with CRC and identified the genes and miRNAs related to the prognosis of CRC patients.

Keywords: Colorectal cancer (CRC); RNA-sequencing; competing endogenous RNA (ceRNA); prognosis; weighted gene co-expression network analysis (WGCNA).