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Research Paper|Volume 15, Issue 9|pp 3498—3523

A novel methionine metabolism-related signature predicts prognosis and immunotherapy response in lung adenocarcinoma

Qing-Hua Chang1, Yuan-Cui Zhang1, Dong-Ying Zhang1, Ting Mao2, Ran Chang3, Nan Wang1, Yun Ye4, Zi-Jun Xu5
  • 1Department of Respiratory Medicine, The Affiliated Third Hospital of Jiangsu University, Zhenjiang, China
  • 2Department of Radiology, The Affiliated Third Hospital of Jiangsu University, Zhenjiang, China
  • 3School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
  • 4Department of Nursing, The Affiliated Third Hospital of Jiangsu University, Zhenjiang, China
  • 5Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
* Equal contribution
Received: February 20, 2023Accepted: April 18, 2023Published: May 2, 2023
https://doi.org/10.18632/aging.204687

Copyright: © 2023 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Recent research revealed methionine metabolism as a key mediator of tumor initiation and immune evasion. However, the relationship between methionine metabolism and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unknown. Here, we comprehensively analyzed the genomic alterations, expression patterns, and prognostic values of 68 methionine-related regulators (MRGs) in LUAD. We found that most MRGs were highly prognostic based on 30 datasets including 5024 LUAD patients. Three distinct MRG modification patterns were identified, which showed significant differences in clinical outcomes and TME characteristics: The C2 subtype was characterized by higher immune score, while the C3 subtype had more malignant cells and worse survival. We developed a MethScore to measure the level of methionine metabolism in LUAD. MethScore was positively correlated with T-cell dysfunction and tumor-associated macrophages (TAMs), indicating a dysfunctional TME phenotype in the high MethScore group. In addition, two immunotherapy cohorts confirmed that patients with a lower MethScore exhibited significant clinical benefits. Our study highlights the important role of methionine metabolism in modeling the TME. Evaluating methionine modification patterns will enhance our understanding of TME characteristics and can guide more effective immunotherapy strategies.