Multi-Omics Clustering Reveals Disulfidptosis Typing in Hepatocellular Carcinoma and Correlates with Immune Features

Abstract

Abstract Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. This study aimed to explore the potential of disulfidptosis, a novel form of cell death, as a prognostic and therapeutic marker in HCC.We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. The low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Five key signature genes (SLC7A11, SLC2A1, ADAM9, ITGAV, and PFKP) were identified to distinguish between the subgroups, and the constructed model exhibited high accuracy. The study also investigated the association of disulfidptosis with microsatellite instability, tumor immune microenvironment, and genomic mutational burden. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. The key genes SLC7A11 and SLC2A1 were identified as crucial for molecular typing and had excellent predictive power for patient survival. RT-qPCR was used to determine the mRNA levels of the two key genes mentioned above. Classification is a highly effective tool for predicting the prognosis and therapeutic response of patients, providing a valuable reference for accurate individualized treatment. The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets.