Disulfidptosis, a recently identified mode of cellular demise marked by excess SLC7A11-reliant cystine, has been proved to affect the development and resilience of tumor cells through the production of glutathione from cystine. Glutathione synthesis plays a crucial role in chemotherapy resistance and the survival of liver cancer cells. Thus, understanding the relationship between disulfidptosis and hepatocellular carcinoma (HCC) is imperative. A molecular typing approach was employed to classify patients with HCC into two distinct subtypes, namely disulfidptosis and disulfide-homeostasis, based on the expression of genes associated with disulfidptosis. Patients with disulfidptosis exhibited a longer survival time, improved immune status, and heightened sensitivity to conventional chemotherapeutic drugs and immunotherapy. Patients with disulfide-homeostasis demonstrated an immunosuppressive microenvironment, drug resistance, and unfavorable prognosis. A prognostic model was constructed utilizing the significant prognostic variables of the disulfidptosis-regulated genes. A real-world cohort was subjected to multiplex immunofluorescence to validate the clinical outcomes and immune context. Ultimately, our study delved into the prognostic relevance of disulfidptosis in HCC and provides insights into potential avenues for future research.
Keywords: Disulfidptosis; Hepatocellular carcinoma; Molecular subtype; Prognostic model; Tumor microenvironment.
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