Action of m6A-related gene signatures on the prognosis and immune microenvironment of colonic adenocarcinoma

Han Shugao; Wu Yinhang; Zhuang Jing; Qu Zhanbo; Da Miao

Heliyon (Jun 2024)

Action of m6A-related gene signatures on the prognosis and immune microenvironment of colonic adenocarcinoma

Han Shugao,
Wu Yinhang,
Zhuang Jing,
Qu Zhanbo,
Da Miao

Affiliations

Han Shugao: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
Wu Yinhang: Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China; Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, Huzhou, China
Zhuang Jing: Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China; Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, Huzhou, China
Qu Zhanbo: Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China; Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, Huzhou, China
Da Miao: Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, China; Corresponding author. No.2088, East Tiaoxi Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.

Journal volume & issue: Vol. 10, no. 11
p. e31441

Abstract

Read online

N6-methyladenosine (m6A) modification in human tumor cells exerts considerable influence on crucial processes like tumorigenesis, invasion, metastasis, and immune response. This study aims to comprehensively analyze the impact of m6A-related genes on the prognosis and immune microenvironment (IME) of colonic adenocarcinoma (COAD). Public data sources, predictive algorithms identified m6A-related genes and differential gene expression in COAD. Subtype analysis and assessment of immune cell infiltration patterns were performed using consensus clustering and the CIBERSORT algorithm. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis determined gene signatures. Independent prognostic factors were identified using univariate and multivariate Cox proportional hazards models. The findings indicate that 206 prognostic m6A-related DEGs contribute to the m6A regulatory network along with 8 m6A enzymes. Based on the expression levels of these genes, 438 COAD samples from The Cancer Genome Atlas (TCGA) were classified into 3 distinct subtypes, showing marked differences in survival prognosis, clinical characteristics, and immune cell infiltration profiles. Subtype 3 and 2 displayed reduced levels of infiltrating regulatory T cells and M0 macrophages, respectively. A six-gene signature, encompassing KLC3, SLC6A15, AQP7 JMJD7, HOXC6, and CLDN9, was identified and incorporated into a prognostic model. Validation across TCGA and GSE39582 datasets exhibited robust predictive specificity and sensitivity in determining the survival status of COAD patients. Additionally, independent prognostic factors were recognized, and a nomogram model was developed as a prognostic predictor for COAD. In conclusion, the six target genes governed by m6A mechanisms offer substantial potential in predicting COAD outcomes and provide insights into the unique IME profiles associated with various COAD subtypes.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

About the journal

Abstract

Keywords