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Methylation Pattern Mediated by m6A Regulator and Tumor Microenvironment Invasion in Lung Adenocarcinoma

Feng Jiang1, Yifang Hu2, Xiaoqin Liu3

  • 1Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.

Oxidative Medicine and Cellular Longevity
|January 17, 2022
PubMed
Abstract

Insights

RNA N6-methyladenosine (m6A) alterations are crucial in shaping the tumor microenvironment (TME). Understanding m6A patterns can predict tumor inflammation, subtype, and prognosis, guiding immunotherapy strategies.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Immunology

Background:

  • Epigenetic modifications influence immune responses.
  • The role of RNA N6-methyladenosine (m6A) alterations in tumor microenvironment (TME) cell invasion remains largely unexplored.

Purpose of the Study:

  • To investigate the patterns of m6A alteration in lung adenocarcinoma (LUAD).
  • To correlate m6A modification patterns with TME cell invasion characteristics and clinical outcomes.

Main Methods:

  • Analysis of 23 m6A regulators in 629 LUAD tissues.
  • Quantification of m6A modification patterns using principal component analysis to derive an m6A score.
  • Verification of m6A-related enzymes and the hub gene NOL10 in lung cancer cell lines.

Main Results:

  • Identified three distinct m6A alteration modes correlating with tumor immunological phenotypes (rejection, inflammation, desert).
  • A high m6A score indicates TME inflammation, elevated mutation load, immune activation, and increased neoantigen burden, associated with better therapeutic response.
  • Low m6A subtype shows matrix activation, poor immune infiltration, and reduced survival probability.

Conclusions:

  • m6A alterations are critical in establishing TME complexity and invasion features.
  • Analyzing single-tumor m6A patterns can enhance understanding of TME and inform immunotherapy strategies.
  • Targeting the hub gene NOL10 significantly inhibited lung cancer cell growth and migration.

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