AUTHOR=Song Wei , Ren Jun , Wang Chuntao , Ge Yuhang , Fu Tao 

TITLE=Analysis of Circular RNA-Related Competing Endogenous RNA Identifies the Immune-Related Risk Signature for Colorectal Cancer

JOURNAL=Frontiers in Genetics

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00505

DOI=10.3389/fgene.2020.00505

ISSN=1664-8021

ABSTRACT=Background: Recent papers have described circular RNAs (circRNAs) play important roles in the development and progression of colorectal cancer (CRC). However, the expression profiles of circRNAs and their functions in CRC have rarely been studied. The aim of present study was to identify circRNAs involved in the carcinogenesis and progression of CRC and to explore potential molecular mechanisms as a competitive endogenous RNA (ceRNA). Moreover, we aimed to establish an immune-related gene signature to predict overall survival (OS) in patients with CRC.
Methods: The expression patterns of circRNA, miRNA, mRNA, and clinicopathological data were collected from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. A ceRNA network would be established, and the functional enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed and hubgenes were identified using cytohub plugin. Subsequently, an immune-related signature was developed based on mRNAs in the ceRNA network. Finally, a prognostic nomogram combining the immune-related risk score and clinicopathological characteristics was developed. 
Results: We established a circRNA-miRNA-mRNA ceRNA network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the mRNAs were mainly enriched in neuroactive ligand-receptor interaction, Wnt signaling pathway, cell adhesion molecules, and renin secretion. PPI network and module analysis identified 10 hubgenes, and the circRNA-miRNA-hubgene regula¬tory modules was established. After univariate and multivariate analysis, 7 immune-related genes in the ceRNA network were used to construct immune-related signature. Patients were divided into high- and low-risk groups, and patients with high-risk had significantly shorter OS than low-risk patients. The ROC curve showed good performance in survival prediction. Furthermore, we established a prognostic nomogram based on immune-related risk score and clinicopathologic factors. The areas under the curve (AUC) and calibration curves indicated that the nomogram showed well accuracy of prediction. In addition, high-risk score was positively correlated with six immune infiltrating cells (P < 0.05).
Conclusions: We screened the key genes and established a circRNA-related ceRNA network involved in CRC, which will assist in understanding the molecular mechanisms underlying the carcinogenesis and progression. Moreover, our proposed immune-based signature may predict survival and reflect the immune status of CRC patients.