Interplay of disulfidptosis and the tumor microenvironment across cancers: implications for prognosis and therapeutic responses
Shengshan Xu, Zizhou Chen, Xiguang Chen, Hongyu Chu, Xufeng Huang, Chunyu Chen, Hejie Liu, Ying Qu, Zhuming Lu
Abstract
The recent elucidation of disulfidptosis, a unique form of cell death, has opened new paths for the development of targeted cancer therapies. However, a thorough examination of disulfidptosis-related genes (DRGs) across various cancer types has been lacking. Our extensive analysis of DRGs through genomic, transcriptional, and immune profiling has yielded substantial insights. Utilizing The Cancer Genome Atlas (TCGA), we have identified key changes in gene expression, including alterations in copy number and DNA methylation, and evaluated their impact on cancer prognosis. We constructed a disulfidptosis-related signature (DFRS) using LASSO regression and multivariate Cox regression analysis, which demonstrated a strong prognostic connection across diverse cancer types. The DFRS score is linked with poorer clinical outcomes, reflects the immune characteristics of the tumor microenvironment (TME), and predicts responsiveness to immunotherapy and other treatments. Notably, the DFRS score interacts with critical oncogenic pathways, highlighting the potential benefits of targeting disulfidptosis in cancer treatment. Our findings underscore the critical influence of disulfidptosis on cancer prognosis and therapeutic response, offering meaningful clinical insights.