尽管奥西美替尼的使用能显著提高具有表皮生长因子受体突变的肺腺癌（LUAD）患者的生存时间，然而药物抗性最终会限制大多数患者的生存益处。本研究旨在基于与奥西美替尼抗性相关的基因开发一种新的预后预测标识。从Gene Expression Omnibus数据集和The Cancer Genome Atlas数据集中筛选与奥西美替尼抗性相关的差异表达基因（DEGs）。使用多变量Cox回归建立预后标识，然后开发一种预测LUAD患者生存概率的评分卡。我们使用ROC曲线和DCA曲线评估其临床预测准确性和净益。此外，选择与预后显著相关的差异表达基因进行免疫渗透分析和药物敏感性分析，并通过体外实验验证其在肺腺癌发展中的作用。我们的评估结果表明，新的评分卡的临床预测准确性和净益值高于TN评分卡。进一步分析显示，STRIP2表达低的患者具有更高的免疫应答水平，可能更有可能从免疫检查点抑制剂和常规抗肿瘤药物中获益。这可以帮助为奥西美替尼抗性的LUAD患者选择更精准和适当的治疗。此外，体外实验显示STRIP2促进了LUAD细胞的增殖、迁移和侵袭。这进一步证明了该基因标识对预后预测的重要性。我们基于与奥西美替尼抗性相关的DEGs开发了一个可靠的预后模型，并筛选了可以预测LUAD患者免疫应答的生物标志物，这可能有助于在奥西美替尼抗性后选择治疗方案。© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Although the use of osimertinib can significantly improve the survival time of lung adenocarcinoma (LUAD) patients with epithelial growth factor receptor mutation, eventually drug resistance will limit the survival benefit of most patients. This study aimed to develop a novel prognostic predictive signature based on genes associated with osimertinib resistance.The differentially expressed genes (DEGs) associated with osimertinib resistance in LUAD were screened from Gene Expression Omnibus datasets and The Cancer Genome Atlas datasets. Multivariate cox regression was used to establish a prognostic signature, and then a nomogram was developed to predict the survival probability of LUAD patients. We used ROC curve and DCA curve to evaluate its clinical prediction accuracy and net benefit. In addition, the differentially expressed genes significantly associated with prognosis were selected for immune infiltration analysis and drug sensitivity analysis, and their roles in the progression of lung adenocarcinoma were verified by in vitro experiments.Our evaluation results indicated that the new nomogram had higher clinical prediction accuracy and net benefit value than the TN nomogram. Further analysis showed that patients with low STRIP2 expression had a higher level of immune response, and may be more likely to benefit from immune checkpoint inhibitors and conventional antitumor drugs. This may help to select more precise and appropriate therapy for LUAD patients with osimertinib resistance. Furthermore, in vitro experiments showed that STRIP2 promoted the LUAD cells proliferation, migration and invasion. This further demonstrates the importance of this gene signature for prognostic prediction.We developed a reliable prognostic model based on DEGs associated with osimertinib resistance and screened for biomarker that can predict the immune response in LUAD patients, which may help in the selection of treatment regimens after osimertinib resistance.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.