Osimertinib resistance-based immune prognostic related gene signature in EGFR mutant lung adenocarcinoma, in which PSMD11 promotes tumor progression

作者：Yuquan Bai, Xu He, Peilong Bao, Yang Gao, Jingwei Sun, Yang Shen, Jinbo Zhao, Tao Jiang · 发表于：Translational Lung Cancer Research · 年份：2025 · DOI：10.21037/tlcr-2025-355 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、Cytokine Signaling Pathways and Interactions

Background: At present, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment, as the first-line treatment of lung adenocarcinoma (LUAD) with EGFR mutation, has achieved good clinical efficacy, but most patients will eventually develop acquired resistance. The objective of this study is to accurately identify drug-resistant LUAD patients who can benefit from other treatments by constructing a predictive model for EGFR-TKIs resistance. Methods: via western blot and immunohistochemistry. Results: T cells, M0/M1 macrophages, and natural killer (NK) cells. In addition, knockdown of PSMD11 could inhibit cell proliferation, promote cell apoptosis, and increase the sensitivity of drug-resistant cells to OSI. And compared with individual treatment, the combination treatment of PSMD11-siRNA and OSI in PC9OR and H1975OR cells could significantly inhibit cell proliferation and tumor growth. In addition, PSMD11 could promote the progression of OSI-resistant LUAD by activating the NF-κB/IL-6/STAT3 signaling pathway. Conclusions: This signature has a high predictive effect on the prognosis of OSI-resistant LUAD patients, and can be used as a powerful predictive tool for further selection of chemotherapy and immunotherapy in OSI-resistant LUAD patients.