肺腺癌（LUAD）仍然是全球最致命的恶性肿瘤之一，死亡率高且预后不良。内质网（ER）应激是肿瘤生长、转移以及化疗、靶向治疗和免疫反应的关键调节因子。它通过响应错误折叠的蛋白质并触发内质网应激传感器和下游信号通路的异常激活来发挥作用。值得注意的是，内质网应激相关基因 (ERSRG) 的表达模式可以指示生存结果，尤其是在免疫浸润的情况下。通过对与预后相关的 ERSRG 进行共识聚类，我们描绘了两种不同的 LUAD 亚型：簇 1 和簇 2。综合分析显示这些亚型在预后、免疫细胞浸润和肿瘤进展方面存在显着差异。利用 LASSO 回归和多元逐步回归的稳健性，我们构建并验证了 LUAD 的 ER 压力相关风险特征。该特征接受了其预后价值、与临床属性的相关性以及肿瘤免疫微环境内的相互作用的评估。通过将此特征与不同病理阶段的多变量 cox 分析相结合，我们设计了一个增强的列线图，并通过各种统计指标进行验证，诊断后 1 年、3 年和 5 年总生存率的曲线下面积分别为 0.79、0.80，和0.81，分别。总之，我们的研究结果介绍了 11 个关键 ERSRG 的综合特征，有望成为 LUAD 的有效预后工具，并为免疫治疗和靶向干预策略提供见解。© 2023。作者。

Lung adenocarcinoma (LUAD) remains one of the most lethal malignancies worldwide, with a high mortality rate and unfavorable prognosis. Endoplasmic reticulum (ER) stress is a key regulator of tumour growth, metastasis, and the response to chemotherapy, targeted therapies and immune response. It acts via responding to misfolded proteins and triggering abnormal activation of ER stress sensors and downstream signalling pathways. Notably, the expression patterns of ER-stress-related-genes (ERSRGs) are indicative of survival outcomes, especially in the context of immune infiltration. Through consensus clustering of prognosis-associated ERSRGs, we delineated two distinct LUAD subtypes: Cluster 1 and Cluster 2. Comprehensive analyses revealed significant disparities between these subtypes in terms of prognosis, immune cell infiltration, and tumor progression. Leveraging the robustness of LASSO regression and Multivariate stepwise regression, we constructed and validated an ER Stress-associated risk signature for LUAD. This signature underwent assessments for its prognostic value, correlation with clinical attributes, and interaction within the tumour immune microenvironment. By integrating this signature with multivariate cox analysis of distinct pathological stages, we devised an enhanced nomogram, validated through various statistical metrics, with an area under the curve for overall survival at 1, 3, and 5 years post-diagnosis being 0.79, 0.80, and 0.81, respectively. In conclusion, our findings introduce a composite signature of 11 pivotal ERSRGs, holding promise as a potent prognostic tool for LUAD, and offering insights for immunotherapeutic and targeted intervention strategies.© 2023. The Author(s).