M6A Methylation Regulators METTL3 and ALKBH5 are Risk Factors for EGFR-Mutant NSCLC - Article abstract

Sep 23, 2026

Non-small cell lung cancer (NSCLC) represents over 85% of lung cancers, and EGFR-TKI therapy commonly faces inevitable drug resistance. This retrospective study evaluates whether m6A methylation regulators relate to EGFR mutations and their clinical significance. m6A-related regulatory factors are measured across EGFR-mutant and EGFR-wildtype NSCLC specimens using retrospective datasets and immunohistochemistry. Results show EGFR-mutant cases have higher METTL3 and ALKBH5 expression, with high levels independently linked to shorter progression-free survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusions

M6A Methylation Regulators METTL3 and ALKBH5 are Risk Factors for EGFR-Mutant NSCLC Cancer Control Volume 32: 1-13 © The Author(s) 2025 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI: 10.1177/10732748251342685](DOI: 10.1177/10732748251342685) [journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx) Yaofeng Zhi, MMed 1,* 􀀁, Silin Liu, MMed1,2,* 􀀁, Xuefei Chang, MMed1,2 􀀁 , Wanxian Guan, MMed 1,2 􀀁, Ronggang Li, MMed3 􀀁, Qiongru Liu, BSc3 􀀁 , Jiaqing Chen, MSc 1 􀀁, Jie Ling, BSc1 􀀁, Xulin Zhao, BSc1 􀀁, Aibin Liu, MD4,5 􀀁 , Jiarong Chen, MD 1,6 􀀁, Xin Zhang, MD1,7,8 􀀁, and Yanming Huang, MMed1,3 􀀁 Abstract Introduction: Non-small cell lung cancer (NSCLC), which accounts for >85% of all lung cancers, is the most common solid malignant tumor, with high morbidity and mortality worldwide. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment is widely used clinically because the epidermal growth factor receptor (EGFR) is the main driver gene of lung cancer; however, the development of drug resistance is inevitable. Epigenetic abnormalities can also lead to tyrosine kinase inhibitor (TKI) resistance. However, the relationship between N6-methyladenosine (m6A)-related proteins and EGFR mutations in NSCLC and their clinical signiﬁcance remain unclear. In this retrospective study, the expression of m6A-related regulatory factors in patients with EGFR mutations were analyzed to investigate their relationship with clinicopathological features and prognoses. Methods: The association between m6A-related regulatory factors and NSCLC was analyzed using data derived from The Cancer Genome Atlas, case collection, follow-up, immunohistochemistry, and scoring. Results: A total of 246 NSCLC specimens were examined in this study. Among these, 143 EGFR-mutant cases exhibited signiﬁcantly higher expression of METTL3 and ALKBH5 compared to EGFR-wildtype specimens. The median progression-free survival time of patients with high METTL3 expression (SI >6) was 25.0 months, and that of patients with high ALKBH5 expression (SI >6) was 24.1 months in EGFR-mutant cases. High METTL3 and ALKBH5 expression levels are independent risk factors for progression-free survival in patients with EGFR mutations. The median progression-free survival time 1 Clinical Experimental Center, Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational Research, Jiangmen Key Laboratory of Precision and Clinical Translation Medicine, Jiangmen Central Hospital, China 2Department of Pulmonary and Critical Care Medicine, Jiangmen Central Hospital, China 3Department of Pathology, Jiangmen Central Hospital, China 4Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China 6Department of Oncology, Jiangmen Central Hospital, China 7Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China 8Collaborative Innovation Center for Antitumor Active Substance Research and Development, Guangdong Medical University, Zhanjiang, China *Yaofeng Zhi and Silin Liu contribute equally to this research. Corresponding Authors: Xin Zhang, Jiangmen central Hospital, No.23 of Haibang Street, Jiangmen, Guangdong 529030, China. Email: [zhangx45@mail3.sysu.edu.cn](zhangx45@mail3.sysu.edu.cn) Yanming Huang, Jiangmen Central Hospital, No.23 of Haibang Street, Jiangmen, Guangdong 529030, China. Email: [huangyanming_jxy@163.com](huangyanming_jxy@163.com) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licen

FAQs

What is the main question of the study?

The study examines whether m6A-related proteins, especially METTL3 and ALKBH5, are associated with EGFR mutations in NSCLC and what clinical significance they have.

How were m6A-related regulators assessed?

Associations were analyzed using datasets including The Cancer Genome Atlas, case collection and follow-up, together with immunohistochemistry and scoring.

What did the study find about METTL3 and ALKBH5?

EGFR-mutant NSCLC specimens showed significantly higher METTL3 and ALKBH5 expression than EGFR-wildtype specimens. High METTL3 and ALKBH5 expression were independent risk factors for progression-free survival.

Sep 23, 2026

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