Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma

Abstract

Abstract Cisplatin resistance remains a significant barrier in treating lung adenocarcinoma (LUAD). While the search for predictive biomarkers in LUAD prognosis has seldom focused on cisplatin resistance genes. In this study, we analyzed 181 cisplatin resistance genes from LUAD-related cell lines RNA sequences data using the TCGA and GEO databases, identifying two pivotal genes, E2F7 and FAM83A. Utilizing these genes, we established comprehensive models for diagnosis, prognosis, and recurrence risk in LUAD. Notably, our analysis revealed that the high-risk group, as defined by these models, displayed elevated levels of CD4 + T cells and CD8 + T cells, along with increased expression of PD-L1 and PD-L2, compared to their low-risk counterparts. Our in vitro studies demonstrated that inhibiting E2F7 in lung cancer cells significantly inhibited cell proliferation, decreased cell migration and invasion, while also increasing apoptosis rates. Corresponding in vivo experiments indicated that E2F7 knockdown suppressed tumor growth and lung metastasis in both subcutaneous tumor-bearing and tail-vein metastasis models. These findings underscore the diagnostic and prognostic efficacy of our E2F7 and FAM83A-based models, paving the way for more personalized treatment approaches in LUAD.