Characterization of a ferroptosis-related gene signature predicting survival and immunotherapeutic response in lung adenocarcinoma.

Abstract

Lung cancer remains the leading cause of cancer-related death worldwide, and drug resistance represents the main obstacle responsible for the poor mortality and prognosis. Here, to identify a novel gene signature for predicting survival and drug response, we jointly investigated RNA sequencing data of lung adenocarcinoma patients from TCGA and GEO databases, and identified a ferroptosis-related gene signature. The signature was validated in the validation set and two external cohorts. The high-risk group had a reduced survival than the low-risk group (P < 0.05). Moreover, the established gene signature was associated with tumor mutation burden, microsatellite instability, and response to immune checkpoint blockade. In addition, four candidate oncogenes (RRM2, SLC2A1, DDIT4, and VDAC2) were identified to be candidate oncogenes using in silico and wet experiments, which could serve as potential therapeutic targets. Collectively, this study developed a novel ferroptosis-related gene signature for predicting prognosis and drug response, and identified four candidate oncogenes for lung adenocarcinoma.