目的  建立免疫原性细胞死亡（ICD）相关基因标志物体系，揭示其对肺腺癌免疫浸润和预后的调控机制。方法  基于癌症基因组图谱（TCGA）和基因表达总库（GEO）数据库分析肺腺癌（LUAD）中ICD基因表达谱，通过加权基因共表达网络分析（WGCNA）筛选差异表达的ICD相关基因（ICD-RGs）集，建立LASSO-Cox预后模型并开展功能与药物敏感性分析；体外验证BI-2536对LUAD细胞增殖、迁移的抑制作用，并通过3例临床样本的Western blotting验证ICD-RGs表达。结果  ICD相关亚型的差异基因主要富集于氨酰基-转运RNA（tRNA）生物合成，三羧酸循环，碱基切除修复，氧化磷酸化，蛋白质出口，剪接体，抗原处理和提呈，B细胞受体信号通路，趋化因子信号通路，细胞因子与细胞因子受体的相互作用，自然杀伤细胞介导的细胞毒性及T细胞受体信号通路，|NES|＞1，P＜0.05；ICD相关基因与LUAD患者预后及免疫微环境均有一定相关性（均P＜0.05）；BI-2536对A549和H1650两种细胞的增殖、侵袭和迁移均有抑制作用，P＜0.05；通过网络计算器开发的诺莫图有较好的预测机制，随时间变化的受试者工作特征曲线（ROC）及决策曲线分析（DCA）均显示诺莫图对预后的预测结果较好；人类蛋白质图谱数据库（HPA）和Western blotting中显示ICD相关基因在LUAD组织和正常组织中的表达存在差异，P＜0.05。结论  ICD相关基因与LUAD的免疫和预后有显著关联，BI-2536可以作为临床药物抑制LUAD细胞生长迁移和侵袭，介导ICD-RGs通路及生物功能活性。此外，新开发的诺莫图为预测LUAD患者的总生存率提供了一种更方便、更准确的方法。

Objective  To investigate the immunogenic cell death-related gene markers mediating immune infiltration and poor prognosis in lung adenocarcinoma. Methods  Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we analysed the expression profile of immunogenic cell death (ICD) genes in lung adenocarcinoma (LUAD), screened for the set of differentially expressed ICD-related genes (ICD-RGs) by weighted gene co-expression network analysis (WGCNA), established the LASSO-Cox prognostic model and carried out the functional and drug sensitivity analysis; in vitro validation of the inhibitory effect of BI-2536 on the proliferation and migration of LUAD cells, and verification of the expression of ICD-RGs by Western blotting of three clinical samples. Results  Differential genes of ICD-related subtypes were mainly enriched in aminoacyl-transfer RNA(tRNA) biosynthesis, citric acid cycle, base excision repair, oxidative phosphorylation, protein export, spliceosome, antigen processing and presentation, B-cell receptor signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interactions, natural killer cell-mediated cytotoxicity, and T-cell receptor signaling pathway, |NES|>1, P<0.05; ICD-RGs were significantly associated with both prognosis and immune microenvironment in LUAD patients (all P<0.05); BI-2536 had an inhibitory effect on the proliferation, invasion, and migration of both A549 and H1650 cells, P<0.05; Nomograms developed through the network calculator had a better predictive mechanism, and both receiver operating characteristic(ROC) and decision curve analysis(DCA) over time showed that nomograms were better predictors of prognosis; ICD-RGs showed differential expression in LUAD tissues and normal tissues in Human Protein Atlas(HPA) and Western blotting. Conclusion  ICD-RGs are significantly associated with immunity and prognosis of LUAD, and BI-2536 can be used as a clinical drug to inhibit the growth migration and invasion of LUAD cells, mediate the ICD-RGs pathway and biofunctional activity. In addition, the newly developed nomogram provides a more convenient and accurate method to predict the overall survival of LUAD patients.