Li Long, He Shancheng
Department of Critical Care Medicine, The Fifth People's Hospital of Ganzhou City, Ganzhou, 341000, China.
Ganzhou Key Laboratory of Respiratory Diseases, Ganzhou, 341000, China.
Discov Oncol. 2024 Dec 23;15(1):828. doi: 10.1007/s12672-024-01736-0.
Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell death (PCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, in shaping LUAD heterogeneity, immune infiltration, and prognosis. Among these, ferroptosis and pyroptosis were most significantly associated with favorable survival outcomes, highlighting their potential roles in enhancing anti-tumor immunity. Distinct PCD-related LUAD subtypes were identified, characterized by differential pathway activation and immune cell composition. Subtypes enriched with cytotoxic lymphocytes and dendritic cells demonstrated improved survival outcomes and increased potential responsiveness to immunotherapy. Drug sensitivity analysis revealed that these subtypes exhibited heightened sensitivity to targeted therapies and immune checkpoint inhibitors, suggesting opportunities for personalized treatment strategies. Our findings emphasize the interplay between PCD pathways and the tumor microenvironment, providing insights into the mechanisms underlying tumor drug resistance and immune evasion. By linking molecular and immune features to clinical outcomes, this study highlights the potential of targeting PCD pathways to enhance therapeutic efficacy and overcome resistance in LUAD. These results contribute to a growing framework for developing precise and adaptable cancer therapies tailored to specific tumor characteristics.
肺腺癌（LUAD）是癌症相关死亡的主要原因，其显著的肿瘤异质性以及克服耐药性方面持续存在的挑战是其特征。在本研究中，我们利用单细胞RNA测序（scRNA-seq）来剖析程序性细胞死亡（PCD）途径，包括凋亡、坏死性凋亡、焦亡和铁死亡，在塑造LUAD异质性、免疫浸润和预后方面的作用。其中，铁死亡和焦亡与良好的生存结果最显著相关，突出了它们在增强抗肿瘤免疫中的潜在作用。我们鉴定出了不同的与PCD相关的LUAD亚型，其特征在于不同的途径激活和免疫细胞组成。富含细胞毒性淋巴细胞和树突状细胞的亚型显示出更好的生存结果以及对免疫治疗的潜在反应性增加。药物敏感性分析表明，这些亚型对靶向治疗和免疫检查点抑制剂表现出更高的敏感性，提示了个性化治疗策略的机会。我们的研究结果强调了PCD途径与肿瘤微环境之间的相互作用，为肿瘤耐药性和免疫逃逸的潜在机制提供了见解。通过将分子和免疫特征与临床结果联系起来，本研究突出了靶向PCD途径以提高治疗效果和克服LUAD耐药性的潜力。这些结果为制定针对特定肿瘤特征的精确且适应性强的癌症治疗方法的不断发展的框架做出了贡献。
