ArticleTranslational lung cancer research2025
Osimertinib resistance-based immune prognostic related gene signature in EGFR mutant lung adenocarcinoma, in which PSMD11 promotes tumor progression.
Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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: Based on the differentially expressed genes (DEGs) between osimertinib (OSI)-resistant cells (PC9OR, H1975OR) and OSI-sensitive LUAD cells (PC9, H1975), the EGFR mutant LUAD prognosis-related genes from The Cancer Genome Atlas (TCGA), and the immune genes from ImmPort and InnateDB websites, we constructed an immune prognosis model of OSI resistance to predict the outcome of EGFR mutant LUAD patients. Then, according to the risk score, EGFR mutant LUAD patients were divided into high- and low-risk groups, and the molecular, immune characteristics, and responsiveness to chemotherapy and targeted drugs were analyzed. Next, PSMD11 was knocked down using small interfering RNA (siRNA) to evaluate the effects of PSMD11 on PC9OR and H1975OR cells. Finally, the correlation between PSMD11 and OSI resistance was determined Results: We constructed an immune prognostic prediction model consisting of four OSI-resistant genes ( 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.
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