ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1572810
This article is part of the Research TopicRNA Modifications in Cancer: Unraveling Roles and Therapeutic Potential in Immunity and ImmunotherapyView all 11 articles
Cross-talk of m 6 A Methylation Modification and the tumor microenvironment Composition in esophageal cancer
Provisionally accepted
- 1Hubei University of Medicine, Shiyan, China
- 2Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, Shanghai, China
- 3Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China
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Background: Esophageal cancer (EC) remains a significant clinical challenge, characterized by its aggressive nature and poor prognosis. Current therapeutic strategies, including targeted therapies, have limitations due to the complex interplay between tumor heterogeneity and the tumor microenvironment (TME). However, the specific contributions of N6-methyladenosine (m 6 A) methylation to the TME in EC are yet to be fully elucidated.Methods: Through comprehensive bioinformatics analyses, a detailed examination of m 6 A regulators were conducted in EC using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Single-cell RNA sequencing (scRNA-seq) and a consensus clustering algorithm was employed to classify m 6 A modification patterns and analyzed their relationships with immune cell infiltration and clinical outcomes. Additionally, an m 6 A scoring system was developed based on principal component analysis to assess the prognostic value of identified m 6 A modification patterns.The findings reveal two distinct m 6 A modification clusters associated with divergent TME characteristics and immune infiltration profiles. Patients exhibiting the immune-inflamed phenotype (m 6 A cluster B) demonstrated significantly improved survival compared to those with the immune-excluded phenotype (m 6 A cluster A). Notably, m 6 A scores correlated positively with immune cell presence and related with adverse prognostic outcomes, indicating their potential as predictive biomarkers for immunotherapy responses. A low m 6 A score indicated a better response to immunotherapy.This study highlights the critical role of m 6 A methylation in shaping the TME and influencing immune dynamics in EC. The m 6 A score developed herein provides a novel quantitative tool for predicting tumor behavior and treatment efficacy, paving the way for more personalized immunotherapeutic strategies in clinical practice. This scoring system illustrates a strong correlation with TME immune cell composition, suggesting potential as a biomarker for targeted therapeutic strategies.
Keywords: esophagus cancer, m 6 A, Tumor Microenvironment, Immunotherapy, prognosis, Immune infiltration
Received: 07 Feb 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Sun, Song, Ye, Zhang, Li, Cao, Feng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Min Sun, Hubei University of Medicine, Shiyan, China
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