Molecular subtypes and prognostic signature rooted in disulfidptosis highlight tumor microenvironment in lung adenocarcinoma

作者：Wei Xia, Liu Jiwei, Ruo Chen, Junjie Feng, Lei Wu, Wang Yize, Wang Xiaokun, Chenghu Song, Mao Wenjun · 发表于：Chinese Journal of Cancer Research · 年份：2025 · DOI：10.21147/j.issn.1000-9604.2025.05.11 · 被引用次数：30 · 研究领域：Ferroptosis and cancer prognosis、Lung Cancer Research Studies、Cancer Immunotherapy and Biomarkers

Objective A highly aggressive and lethal malignancy, characterized by its heterogeneity, lung adenocarcinoma (LUAD) presents significant challenges in prognosis and treatment. Disulfidptosis, a newly identified form of regulated cell death, offers novel insights into cancer progression, yet its role in LUAD remains poorly understood. Methods We identified disulfidptosis-related genes (DRGs) from prior studies and analyzed their interactions and functional enrichment. Molecular subtypes were identified through consensus clustering based on DRG expression, and a prognostic DRG signature was developed using multivariate Cox regression analysis. A nomogram integrating clinical variables was developed to predict survival. Comprehensive analyses, including single-cell RNA sequencing, immune infiltration, and drug sensitivity, were validated using clinical specimens, LUAD cell lines, Western blotting (WB) and immunohistochemistry (IHC). Results A total of 16 DRGs were identified, classifying LUAD patients into three distinct subtypes with differential survival and immune profiles. A 4-gene signature ( GYS1 , NDUFA11 , NDUFB10 , SLC7A11 ) was used to build a risk score model, demonstrating robust prognostic accuracy. A nomogram combining this signature with clinical features reliably predicted 1-, 3-, and 5-year survival. The signature correlated with immune cell infiltration, with single-cell analysis revealing DRG enrichment in myeloid cells. Notably, SLC7A11 and GYS1 we...