A transcriptomic pan-cancer signature for potential implications in prognosis and treatment based on disulfidptosis-related gene

Abstract

Abstract Background Disulfidptosis is a new type of regulated cell death that involves cytoskeletal collapse, induced by excessive disulfide bond formation. However, understanding of the biological characteristics and clinical significance of disulfidptosis in pan-cancers remains limited. Methods We obtained transcriptome data from TCGA via UCSC Xena. Based on the expression of disulfidptosis-related genes (DRG), we constructed a consensus DRG-related signature (DRGS) using the LASSO Cox regression model. A nomogram incorporating the DRG score was developed as a quantitative tool for predicting prognosis. We utilized the z-score algorithm to integrate gene expression characteristics and activity of specific pathways. Comprehensive analyses were performed to investigate tumor microenvironment and mutation profiles. We evaluated the responses of subgroups to immunotherapy and conducted drug screening. Finally, we utilized immunofluorescence (IF) to evaluate the expression of hub genes in patients with ovarian cancer (OV). Results The DRGS was considered a prognostic factor for various types of cancer, with higher scores indicating more unfavorable outcomes. DRGS can also serve as a predictive indicator for various malignant biological processes. The independent prognostic significance for survival was confirmed using multivariate analysis. The group characterized by high expression levels of inverted formin 2 (INF2) demonstrated an attenuated response to palbociclib treatment and an immunosuppressive phenotype. In OV, INF2 was associated with poor clinical outcomes. Conclusion Our study demonstrated a prognostic DRGS, which holds great promise as a robust tool for uncovering clinical characteristics, predicting survival outcomes, and reflecting the response to targeted therapy across various cancer types.