Identification and validation of disulfidptosis-related subtypes and the prognostic model in hepatocellular carcinoma

Abstract

Abstract Background Disulfidptosis is a newly discovered form of cell death. The latest reports have revealed potential mechanisms for disulfide-mediated cell damage, including actin cytoskeleton proteins and cellular scaffold proteins, which are susceptible to disulfide stress. Accumulation of disulfides in cells results in the breakdown of the actin network and cell death. However, the prognostic role and regulatory mechanism of disulfidptosis-related genes in hepatocellular carcinoma remain unclear. Methods The differential expression, copy number variation, and prognostic relevance of 10 genes associated with disulfidptosis were analyzed. Based on the expression levels of the disulfidptosis-related genes, unsupervised clustering analysis was performed to classify the samples into three subtypes, and their gene expression, biological functions, and immune cell infiltration were analyzed. Subsequently, the common differentially expressed genes were screened and a gene prognostic model was established. Samples with high-risk scores showed higher immune cell infiltration and expression of immune checkpoint genes. Results Firstly, we found that four genes (LRPPRC, NCKAP1, RPN1, SLC7A11) showed significant prognostic ability for overall survival in HCC patients. Subsequently, using consensus clustering analysis, the samples were divided into three clusters(A, B and C cluster) based on the expression levels of the four prognostic disulfidoptosis genes, where the prognostic of B cluster was worse, and the cell cycle pathway activation was significantly enriched. Furthermore, the immune cell infiltration abundance was calculated, significant differences in TME were observed among the three subtypes. Additionally, among the common differentially expressed genes among the three subtypes, lasso regression was used to screen six survival-related genes, and a prognostic model was established. Finally, our results suggest that the risk score may serve as a useful tool for predicting sensitivity to immunotherapy and drug treatment in HCC patients. Conclusion These findings highlight the significant clinical implications of the sulfide death pathway and provide new insights into guiding personalized immune therapy strategies for patients with hepatocellular carcinoma.