The following is a summary of “Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma,” published in the May 2024 issue of Oncology by Mao et al.
Drug resistance presents a formidable challenge in cancer therapy, particularly as a predominant cause of treatment failure. Cisplatin, a cornerstone chemotherapeutic agent for lung adenocarcinoma (LUAD), demonstrates substantial efficacy. However, the emergence of cisplatin resistance significantly impedes therapeutic success. Consequently, identifying genes associated with cisplatin resistance and implementing personalized treatment strategies is imperative for improving patient outcomes.
This study utilized transcriptome data from cisplatin-resistant LUAD cells in the GEO database to identify 181 genes linked to cisplatin resistance. Through a combination of univariate regression analysis, random forest modeling, and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were pinpointed. A prognostic model was then developed, leveraging E2F7 and FAM83A as key biomarkers. The effects of E2F7 on the proliferation, migration, invasiveness, and apoptosis of A549/PC9 cells were assessed using the Cell Counting Kit 8 assay, Transwell assay, and flow cytometry. Additionally, Western blotting was employed to elucidate the impact of E2F7 on the AKT/mTOR signaling pathway.
The results of this study identified E2F7 and FAM83A as critical genes associated with cisplatin resistance and established a comprehensive model to aid in the diagnosis, prognosis, and relapse risk evaluation in LUAD. Analysis indicated that patients classified as high-risk based on these genetic markers exhibited elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnostic significance of E2F7 and FAM83A was further validated through clinical data. Notably, inhibition of E2F7 in lung cancer cells significantly curtailed their proliferation, migration, and invasion while enhancing apoptosis. In vivo experiments corroborated these findings, demonstrating reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models.
In conclusion, the study substantiates the prognostic value of a model based on two differentially expressed genes (DEGs), providing a robust method for predicting the efficacy of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on E2F7 and FAM83A exhibits superior performance. In vitro experiments highlight the antitumor potential of reducing E2F7 levels, which impedes LUAD growth and progression. Further exploration into the molecular mechanisms reveals E2F7’s influence on the AKT/mTOR signaling pathway, emphasizing its therapeutic potential. In the era of personalized medicine, this DEG-based model holds promise for guiding clinical practice and enhancing treatment precision.
Source: cancerci.biomedcentral.com/articles/10.1186/s12935-024-03366-6
The post Cisplatin-Resistance Mechanisms: E2F7’s Impact on LUAD Tumor Progression and Metastasis first appeared on Physician's Weekly.