Competing Endogenous RNA in Colorectal Cancer: An Analysis for Colon, Rectum, and Rectosigmoid Junction.

Lucas Maciel Vieira,João Carlos Setubal,João Batista De Sousa,Maria Emília Machado Telles Walter,Peter F Stadler,Natasha Andressa Nogueira Jorge

doi:10.3389/fonc.2021.681579

Abstract

BackgroundColorectal cancer (CRC) is a heterogeneous cancer. Its treatment depends on its anatomical site and distinguishes between colon, rectum, and rectosigmoid junction cancer. This study aimed to identify diagnostic and prognostic biomarkers using networks of CRC-associated transcripts that can be built based on competing endogenous RNAs (ceRNA).MethodsRNA expression and clinical information data of patients with colon, rectum, and rectosigmoid junction cancer were obtained from The Cancer Genome Atlas (TCGA). The RNA expression profiles were assessed through bioinformatics analysis, and a ceRNA was constructed for each CRC site. A functional enrichment analysis was performed to assess the functional roles of the ceRNA networks in the prognosis of colon, rectum, and rectosigmoid junction cancer. Finally, to verify the ceRNA impact on prognosis, an overall survival analysis was performed.ResultsThe study identified various CRC site-specific prognosis biomarkers: hsa-miR-1271-5p, NRG1, hsa-miR-130a-3p, SNHG16, and hsa-miR-495-3p in the colon; E2F8 in the rectum and DMD and hsa-miR-130b-3p in the rectosigmoid junction. We also identified different biological pathways that highlight differences in CRC behavior at different anatomical sites, thus reinforcing the importance of correctly identifying the tumor site.ConclusionsSeveral potential prognostic markers for colon, rectum, and rectosigmoid junction cancer were found. CeRNA networks could provide better understanding of the differences between, and common factors in, prognosis of colon, rectum, and rectosigmoid junction cancer.

Highlights

Colorectal cancer (CRC) is one of the most common and lethal cancers in the world [1]
We found 140 upregulated and 75 downregulated long noncoding RNAs (lncRNAs), 213 upregulated and 136 downregulated miRNAs, and 1,179 upregulated and 1,906 downregulated protein coding genes (PCGs) (Figure 1A)
We found 46 upregulated and 37 downregulated lncRNAs, 119 upregulated and 99 downregulated miRNAs, and 535 upregulated and 1,532 downregulated PCGs (Figure 1B)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common and lethal cancers in the world [1]. CRC can be classified according to its three major affected sites: colon, rectum, and rectosigmoid junction. Together these make up the large bowel. A tumor site is classified as belonging to the rectosigmoid junction when differentiation between rectum and sigmoid is not possible [3]. CRC tumor site identification is important, due to different treatment strategies: for the colon, radical resection, depending on the stage, combined with chemotherapy is used; for rectum, only radical surgery or neoadjuvant chemorradiation followed or not by radical resection [4]; while for the rectosigmoid junction, the best treatment still remains unknown [5]. This study aimed to identify diagnostic and prognostic biomarkers using networks of CRCassociated transcripts that can be built based on competing endogenous RNAs (ceRNA)

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Conclusion