Xia Lei, Chai Zhuodong, Wei Xiaoying, Wei Yuan, Zeng Daxiong, Jiang Junhong, Li Jing
Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Centre of Soochow University, Suzhou, Jiangsu, China.
Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, Texas, USA.
Cancer Rep (Hoboken). 2025 Sep;8(9):e70344. doi: 10.1002/cnr2.70344.
Epigenetic regulation significantly affects immune responses in lung adenocarcinoma (LUAD). However, the role of RNA N6-methyladenosine (m6A) modification, especially in obstructive sleep apnea-hypopnea syndrome (OSAHS) within LUAD, is not well understood.
This study examined m6A modification patterns in 973 LUAD patients using 23 regulatory genes. Unsupervised clustering categorized patients by m6A profiles, quantified by an m6A score. Associations with clinical outcomes, including survival, immune infiltration, tumor microenvironment, OSAHS incidence, and drug sensitivity, were analyzed.
m6A regulator mutations were linked to LUAD, revealing two distinct modification patterns and three gene clusters, all tied to immune phenotypes and clinical outcomes. Higher m6A scores correlated with lower survival, more frequent OSAHS, and increased immune activity. Patients with high m6A scores were more sensitive to PD-L1/PD-1 inhibitors and Phenformin, while those with low scores responded better to Cisplatin, Epothilone B, and Talazoparib.
Analyses confirmed m6A modification's role in LUAD progression, immune regulation, and outcomes. The m6A score is a valuable prognostic marker associated with survival, OSAHS incidence, and drug sensitivity. These findings highlight m6A's potential as a therapeutic target and biomarker, particularly for LUAD patients with OSAHS.
表观遗传调控显著影响肺腺癌（LUAD）的免疫反应。然而，RNA N6-甲基腺苷（m6A）修饰的作用，尤其是在LUAD中的阻塞性睡眠呼吸暂停低通气综合征（OSAHS）中的作用，尚未得到充分了解。
本研究使用23个调控基因检测了973例LUAD患者的m6A修饰模式。无监督聚类根据m6A谱对患者进行分类，并通过m6A评分进行量化。分析了与临床结局的关联，包括生存、免疫浸润、肿瘤微环境、OSAHS发病率和药物敏感性。
m6A调节因子突变与LUAD相关，揭示了两种不同的修饰模式和三个基因簇，均与免疫表型和临床结局相关。较高的m6A评分与较低的生存率、更频繁的OSAHS和增加的免疫活性相关。m6A评分高的患者对PD-L1/PD-1抑制剂和二甲双胍更敏感，而评分低的患者对顺铂、埃博霉素B和他拉唑帕尼反应更好。
分析证实了m6A修饰在LUAD进展、免疫调节和结局中的作用。m6A评分是一个有价值的预后标志物，与生存、OSAHS发病率和药物敏感性相关。这些发现突出了m6A作为治疗靶点和生物标志物的潜力，特别是对于患有OSAHS的LUAD患者。
