Identification of a novel prognostic signature correlated with epithelial‐mesenchymal transition, N6‐methyladenosine modification, and immune infiltration in colorectal cancer

Abstract

Objective: Colorectal cancer (CRC) is a commonly diagnosed human malignancy worldwide. Both epithelial-mesenchymal transition (EMT) and N6methyladenosine (m6A) modification play a crucial role in CRC development.This study aimed to construct a prognostic signature based on the genes related to EMT and m6A modification.Method: Firstly, the mRNA expression profiling of CRC tissues was analyzed using TCGA and GEO databases. The prognostic hub genes related to EMT and m6A modification were selected using weighted correlation network and cox regression analysis. The prognostic signature was constructed based on hub genes, followed by validation in three external cohorts. Finally, the expression of the representative hub gene was detected in clinical samples, and its biological role was investigated using assays in vivo and in vitro.Results: A prognostic signature was constructed using the following genes: YAP1, FAM3C, NUBPL, GLO1, JARID2, NFKB1, CDKN1B, HOOK1, and GIPC2. The signature effectively stratified the clinical outcome of CRC patients in the training cohort and two validation cohorts. The subgroup analysis demonstrated the signature could identify high-risk population from CRC patients within stage I-II or III-IV, female, male and elder patients. The signature was correlated with the infiltration of some immune cells (such as macrophage and regulatory T cells) and gene mutation counts. Finally, the hub gene GIPC2 was found to be downregulated in CRC tissues and most CRC cells lines. GIPC2 overexpression inhibited the malignant characteristics of CRC cells in vitro and in vivo through upregulating E-cadherin and downregulating N-cadherin, Vimentin, and Snail, while the opposite results were observed for GIPC2 knockdown in CRC cells.

Heat shock factor 1 drives regulatory T-cell induction to limit murine intestinal inflammation

“…TGFβ has been shown previously to upregulate HSF1 in human breast cancer via induction of FAM3C protein 44 . In turn, FAM3C is upregulated under inflammatory conditions such as alveolar echinococcosis 45 Within the colon, FAM3C has been linked to Treg infiltration and increased risk of colorectal cancer 46 . As such, FAM3C may have a role in mediating TGFβ-induced regulation of HSF1 in Tregs in this study.…”

Identification of One-carbon metabolism-related gene signature and Analysis of the role of m6A and miRNAs/circRNAs for colon adenocarcinoma

“…Studies have found that m6A modi cation plays an important role in tumor proliferation, differentiation, invasion, and metastasis, and M6A regulates many aspects of the development of colorectal cancer (CRC) [30,31]. Therefore, it is of great signi cance to study the regulation of m6A in colorectal cancer, to identify new therapeutic targets and potential therapeutic drugs, and to improve the prognosis of CRC patients.…”