Link between m6A modification and infiltration characterization of tumor microenvironment in lung adenocarcinoma.

IF 2.8 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Experimental Biology and Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-02 DOI:10.1177/15353702231214266
Sha Yang, Ke Li, Jiqin Zhang, Jian Liu, Lin Liu, Ying Tan, Chuan Xu
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Abstract

N6-methyladenosine (m6A) RNA methylation plays a pivotal role in immune responses and the onset and advancement of cancer. Nonetheless, the precise impact of m6A modification in lung adenocarcinoma (LUAD) and its associated tumor microenvironment (TME) remains to be fully elucidated. Here, we distinguished distinct m6A modification patterns within two separate LUAD cohorts using a set of 21 m6A regulators. The TME characteristics associated with these two patterns align with the immune-inflamed and immune-excluded phenotypes, respectively. We identified 2064 m6A-related genes, which were used as a basis to divide all LUAD samples into three distinct m6A gene clusters. We applied a scoring system to evaluate the m6A gene signature of the m6A modification pattern in individual patients. To authenticate the categorization significance of m6A modification patterns, we established a correlation between m6A score and TME infiltration profiling, tumor somatic mutations, and responses to immunotherapy. A high level of m6A modification may be associated with the aggressiveness and poor prognosis of LUAD. Further studies should investigate the mechanism of action of m6A regulators and m6A-related genes to improve the diagnosis and treatment of patients with LUAD.

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肺腺癌 m6A 修饰与肿瘤微环境浸润特征之间的联系
N6-甲基腺苷(m6A)RNA甲基化在免疫反应以及癌症的发生和发展中起着关键作用。然而,m6A修饰在肺腺癌(LUAD)及其相关肿瘤微环境(TME)中的确切影响仍有待全面阐明。在这里,我们利用一组 21 个 m6A 调节因子区分了两个不同 LUAD 队列中不同的 m6A 修饰模式。与这两种模式相关的TME特征分别与免疫炎症表型和免疫排斥表型相一致。我们确定了 2064 个 m6A 相关基因,并以此为基础将所有 LUAD 样本分为三个不同的 m6A 基因群。我们应用评分系统对个体患者的 m6A 基因修饰模式特征进行了评估。为了验证m6A修饰模式的分类意义,我们建立了m6A评分与TME浸润图谱、肿瘤体细胞突变和免疫疗法反应之间的相关性。高水平的m6A修饰可能与LUAD的侵袭性和不良预后有关。进一步的研究应探讨m6A调节因子和m6A相关基因的作用机制,以改善LUAD患者的诊断和治疗。
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来源期刊
Experimental Biology and Medicine
Experimental Biology and Medicine 医学-医学:研究与实验
CiteScore
6.00
自引率
0.00%
发文量
157
审稿时长
1 months
期刊介绍: Experimental Biology and Medicine (EBM) is a global, peer-reviewed journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. EBM provides both research and review articles as well as meeting symposia and brief communications. Articles in EBM represent cutting edge research at the overlapping junctions of the biological, physical and engineering sciences that impact upon the health and welfare of the world''s population. Topics covered in EBM include: Anatomy/Pathology; Biochemistry and Molecular Biology; Bioimaging; Biomedical Engineering; Bionanoscience; Cell and Developmental Biology; Endocrinology and Nutrition; Environmental Health/Biomarkers/Precision Medicine; Genomics, Proteomics, and Bioinformatics; Immunology/Microbiology/Virology; Mechanisms of Aging; Neuroscience; Pharmacology and Toxicology; Physiology; Stem Cell Biology; Structural Biology; Systems Biology and Microphysiological Systems; and Translational Research.
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