Crosstalk among disulfidptosis-related lncRNAs in lung adenocarcinoma reveals a correlation with immune profile and clinical prognosis

Abstract

Disulfidptosis refers to a specific programmed cell death process characterized by the accumulation of disulfides. It has recently been reported in several cancers. However, the impact of disulfidptosis-related long non-coding RNAs (lncRNAs) on malignant tumors has remained largely unknown. In the present work, we screened prognostic disulfidptosis-related lncRNAs and studied their effects on lung adenocarcinoma. Relevant clinical data of lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) database. RNA sequencing was used to identify differentially expressed disulfidptosis-related lncRNAs within lung adenocarcinoma. In addition, prognostic disulfidptosis-related lncRNAs were obtained through univariate Cox regression analysis. LASSO-COX was used to construct new disulfidptosis-related lncRNA signatures. Different statistical approaches were used to validate the practicability and accuracy of the disulfidptosis-related lncRNAs signatures. Furthermore, several bioinformatic approaches were used to study relevant heterogeneities in biological processes and pathways of diverse risk groups. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was conducted to analyze the expression of disulfidptosis-related lncRNAs. Finally, seven disulfidptosis-related lncRNA signatures were identified in lung adenocarcinoma cells. The prognosis prediction model constructed efficiently predicted patient survival. Subgroup analysis revealed significant differences in immune cell proportion, including T follicular helper cells and M0 macrophages. In addition, in vitro experimental results demonstrated significant differences in disulfidptosis-related lncRNAs. Altogether, the six disulfidptosis-related lncRNA signatures could serve as a potential prognostic biomarker for lung adenocarcinoma. Furthermore, these can be used as a prediction model in individualized immunotherapy for lung adenocarcinoma.

Keywords: Disulfidptosis; Drug sensitivity; Immunotherapy response; Lung adenocarcinoma; Prognosis.