Development of a disulfidptosis-related lncRNA signature to prognosticate lung adenocarcinoma

Abstract

Abstract Background Identification of disulfidptosis as an innovative mechanism of cell demise activated by disulfide stress offers a promising approach to treating cancer. Recent studies suggest that long non-coding RNAs (lncRNAs) play a pivotal role in regulating programmed cell death as well as the development of lung adenocarcinoma (LUAD). However, it remains unclear whether disulfidptosis-related lncRNAs (DRLs) play a role in LUAD prognosis. Methods Transcriptome and clinical data of 507 LUAD patients were extracted from The Cancer Genome Atlas (TCGA). Prognostic DRLs were identified using Pearson correlations and Cox regression. A prognostic signature was established using LASSO and stepwise regression, and a web-based nomogram was created for dynamic survival prediction. The correlation between immune landscape and DRLs score was assessed, and drug sensitivity was analyzed using the pRRophetic algorithm. Functional assays were performed to investigate the role of LINC02323, a DRL, in LUAD cells. Results The 4 DRLs-signature showed excellent performance in predicting LUAD patients’ survival (AUC1year = 0.742, AUC3years = 0.708, AUC5years = 0.762). Elevated DRLs score was associated with reduced immune score and increased tumor mutation burden. Patients with high riskscore showed higher sensitivity to 5-Fluorouracil, cytarabine, dasatinib, erlotinib, and savolitinib, while those with low riskscore may benefit more from axitinib treatment. Furthermore, LINC02323 exhibited malignant behavior in LUAD cells. Conclusions Our DRLs signature has a promising predictive capability for LUAD progression, offering new insights into individualized treatment.