CAGE，一种癌胚抗原/睾丸癌抗原，最初是从胃癌患者的血清中分离出的。我们之前已经显示了CAGE在耐药化疗和靶向治疗中的作用。本研究的目的是调查CAGE在奥西美坦耐药中的作用，并确定CAGE在肺腺癌患者中的预后价值。通过免疫组化和原位杂交技术检测CAGE与自噬通量在患者中的临床病理学相关性。利用免疫印迹、免疫荧光染色和免疫组化技术分析自噬在奥西美坦耐药中的可能作用。本研究发现免疫组织化学染色（IHC）显示CAGE在超过50%的肺腺癌患者中表达。在获得EGFR-TKIs抗药性后，CAGE的表达量增加。在肺腺癌患者中，CAGE的高表达与较短的总生存期和无进展生存期相关。因此，CAGE介导着奥西美坦耐药并预测肺腺癌患者的不良预后。我们建立了奥西美坦耐药的非小细胞肺癌细胞系（PC-9/OSI），并进行了CAGE介导的奥西美坦耐药的机制研究。与亲本敏感的PC-9细胞相比，PC-9/OSI细胞显示出增加的自噬通量和CAGE表达。与亲本PC-9细胞相比，PC-9/OSI细胞表现出更高的肿瘤生成、转移和血管生成能力。与PC-9/OSI细胞相比，CAGE CRISPR-Cas9细胞系在体外和体内显示出降低的自噬通量、侵袭、迁移潜能和肿瘤生成潜能。CAGE通过调节自噬在癌症发展中发挥重要作用，并且能够预测肺腺癌患者的不良预后。我们的发现提示CAGE作为一个潜在的治疗靶点，用于开发能克服奥西美坦耐药的抗癌药物。© 2023 Springer Nature Limited.

CAGE, a cancer/testis antigen, was originally isolated from the sera of patients with gastric cancers. Previously, we have shown the role of CAGE in resistance to chemotherapy and target therapy. The aim of this study was to investigate the role of CAGE in osimertinib resistance and determine the prognostic value of CAGE in patients with pulmonary adenocarcinomas. The clinicopathological correlation with CAGE and autophagy flux in patients was examined using immunohistochemistry and in situ hybridization. The possible role of autophagy in osimertinib resistance was analyzed using immune blot, immune fluorescence staining and immunohistochemistry. This study found that immunohistochemical staining (IHC) showed CAGE expression in more than 50% of patients with pulmonary adenocarcinomas (pADCs). CAGE expression was increased in pADCs after the acquisition of EGFR-TKIs resistance. High expression of CAGE was correlated with shorter overall survival and progression free survival in patients with pADCs. Thus, CAGE mediates osimertinib resistance and predicts poor prognosis in patients with pADCs. Osimertinib-resistant non-small cell lung cancer cells (PC-9/OSI) were established and mechanistic studies of CAGE-mediated osimertinib resistance were performed. PC-9/OSI cells showed increased autophagic flux and CAGE expression compared with parental sensitive PC-9 cells. PC-9/OSI cells showed higher tumorigenic, metastatic, and angiogenic potential compared with parental PC-9 cells. CAGE CRISPR-Cas9 cell lines showed decreased autophagic flux, invasion, migration potential, and tumorigenic potential compared with PC-9/OSI cells in vitro and in vivo. CAGE plays a crucial role in the cancer progression by modulating autophagy and can predict the poor prognosis of patients with pulmonary adenocarcinomas. Our findings propose CAGE as a potential therapeutic target for developing anticancer drugs that can overcome osimertinib resistance.© 2023. Springer Nature Limited.