Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer

Bin Peng; Yinglin Lin; Gao Yi; Mingzhen Lin; Yao Xiao; Yezhenghong Qiu; Wenxia Yao; Xinke Zhou; Zhaoyu Liu

doi:10.1038/s41598-024-66744-0

Scientific Reports (Jul 2024)

Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer

Bin Peng,
Yinglin Lin,
Gao Yi,
Mingzhen Lin,
Yao Xiao,
Yezhenghong Qiu,
Wenxia Yao,
Xinke Zhou,
Zhaoyu Liu

Affiliations

Bin Peng: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Yinglin Lin: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Gao Yi: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Mingzhen Lin: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Yao Xiao: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Yezhenghong Qiu: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Wenxia Yao: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Xinke Zhou: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University
Zhaoyu Liu: Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, State Key Laboratory of Respiratory Disease, The Fifth Affiliated Hospital, Guangzhou Medical University, The Fifth Clinical College of Guangzhou Medical University

DOI: https://doi.org/10.1038/s41598-024-66744-0
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 19

Abstract

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Abstract The epigenetic regulation of N6-methyladenosine (m6A) has attracted considerable interest in tumor research, but the potential roles of m6A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m6A regulators (including novel anti-readers) was employed to identify m6A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m6A regulator-related patterns were identified through the unsupervised clustering of 56 m6A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m6A-related scoring system was developed to quantify the m6A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m6A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m6A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.

Published in Scientific Reports

ISSN: 2045-2322 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine; Science
Website: https://www.nature.com/srep/

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