Ji Longfei, Wang Binyu, Shi Danfei, Shen Weiyun, Li Xinmin, Li Yong
Department of Clinical Laboratory, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province, China.
Department of Pathology, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province, China.
Respir Res. 2025 Jul 18;26(1):249. doi: 10.1186/s12931-025-03323-5.
Lung adenocarcinoma (LUAD) is one of the most common subtypes of non-small cell lung cancer, and its mortality rate remains high. As a programmed cell death mode closely related to inflammation, pyroptosis has been found to play an important regulatory role in the tumor immune microenvironment and tumor progression in recent years. However, the characteristics and prognostic value of apoptosis in different cell types in LUAD have not been systematically elucidated.
This study integrated single-cell RNA sequencing (scRNA seq), bulk transcriptome data, and clinical information to comprehensively analyze the expression patterns and functional roles of pyroptosis related genes (PRGs) in LUAD. We conducted high-resolution clustering analysis on the GSE189357 single-cell dataset, constructed a protein interaction network, and established a prognostic model in conjunction with iron death related genes. Experimental validation of key genes through RNA sequencing and qPCR.
This study identified 17 different cell types, among which the pyroptosis activity of myeloid dendritic cells and neutrophils was significantly increased. Differentially expressed PRGs are enriched in immune related pathways, such as inflammasome assembly and NOD like receptor signaling pathways. The seven gene prognostic model we constructed (CXCL2, SLC7A5, CAV1, IFNG, EPAS1, TNFAIP3, CYBB) can effectively distinguish high-risk LUAD patients. Functional enrichment analysis revealed that the IL-17 signaling pathway is active in high-risk populations, suggesting that apoptosis may promote the progression of LUAD through immune dysfunction. Immune infiltration and pseudo time trajectory analysis further reveal the close correlation between PRGs expression and the dynamic state of immune cells. RNA sequencing and qPCR confirmed the differential expression of core genes in tumor tissues.
This study developed a single-cell atlas of pyroptosis in LUAD and identified prognostic biomarkers with potential translational value. Our findings reveal the interaction mechanism between pyroptosis, ferroptosis, and tumor immunity, providing new ideas and targets for precise treatment of LUAD.
肺腺癌（LUAD）是非小细胞肺癌最常见的亚型之一，其死亡率仍然很高。近年来，作为一种与炎症密切相关的程序性细胞死亡模式，细胞焦亡已被发现在肿瘤免疫微环境和肿瘤进展中发挥重要的调节作用。然而，LUAD中不同细胞类型的细胞焦亡特征和预后价值尚未得到系统阐明。
本研究整合单细胞RNA测序（scRNA seq）、批量转录组数据和临床信息，全面分析LUAD中细胞焦亡相关基因（PRGs）的表达模式和功能作用。我们对GSE189357单细胞数据集进行了高分辨率聚类分析，构建了蛋白质相互作用网络，并结合铁死亡相关基因建立了预后模型。通过RNA测序和qPCR对关键基因进行实验验证。
本研究鉴定出17种不同的细胞类型，其中髓样树突状细胞和中性粒细胞的细胞焦亡活性显著增加。差异表达的PRGs富集于免疫相关途径，如炎性小体组装和NOD样受体信号通路。我们构建的七个基因预后模型（CXCL2、SLC7A5、CAV1、IFNG、EPAS1、TNFAIP3、CYBB）可以有效区分高危LUAD患者。功能富集分析表明，IL-17信号通路在高危人群中活跃，提示细胞焦亡可能通过免疫功能障碍促进LUAD的进展。免疫浸润和伪时间轨迹分析进一步揭示了PRGs表达与免疫细胞动态状态之间的密切相关性。RNA测序和qPCR证实了肿瘤组织中核心基因的差异表达。
本研究建立了LUAD细胞焦亡的单细胞图谱，并鉴定出具有潜在转化价值的预后生物标志物。我们的研究结果揭示了细胞焦亡、铁死亡和肿瘤免疫之间的相互作用机制，为LUAD的精准治疗提供了新的思路和靶点。
