Molecular subtypes of disulfidptosis-regulated genes and prognosis models for predicting prognosis, tumor microenvironment infiltration, and therapeutic response in hepatocellular carcinoma

作者：Jialin Qu, Hui Guan, Quan Zheng, Fenghao Sun · 发表于：International Journal of Biological Macromolecules · 年份：2024 · DOI：10.1016/j.ijbiomac.2024.129584 · 被引用次数：8 · 研究领域：Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation、Fibroblast Growth Factor Research

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.