Investigating the role of disulfidptosis related genes in radiotherapy resistance of lung adenocarcinoma.

Abstract

Radiotherapy resistance is an important reason for high mortality in lung cancer patients, but the mechanism is still unclear. Dysregulation of cell proliferation and death plays a crucial role in the onset and progression of lung adenocarcinoma (LUAD). In recent times, a novel form of cellular demise called disulfidptosis, has attracted increasing attention. However, it is unclear whether the radiation-related disulfidptosis genes have prognostic role in LUAD. A complete suite of bioinformatics tools was used to analyze the expression and prognostic significance of radiation-related disulfidptosis genes. Afterward, we investigated the predictive significance of the risk signature in tumor microenvironments (TME), somatic mutations, and immunotherapies. In addition, we conducted a series of experiments to verify the expression of differentially expressed radiotherapy related disulfidptosis genes (DERRDGs) in vitro. A total of 88 DERRDGs were found. We constructed and validated a novel prognostic model based on PRELP, FGFBP1, CIITA and COL5A1. The enrichment analysis showed the DERRDG affected tumor prognosis by influencing tumor microenvironments (TME) and immunotherapy. And we constructed nomogram to promote clinical application. In addition, q-PCR confirmed the significant differences in the expression of prognostic genes between A549 irradiation-resistance cell and A549. Finally, western-blot, IHC staining, and small interference experiment suggested that PRELP may be a potential biomarker for radiotherapy resistance, whose low expression was associated with poor outcomes in LUAD patients. This study reveals the signature and possible underlying mechanisms of DERRDGs in LUAD and discovered the key gene PRELP, which helps to identify new prognostic biomarkers and provides a basis for future research.