Identifying disulfidptosis subtypes in hepatocellular carcinoma through machine learning and preliminary exploration of its connection with immunotherapy

作者：Guanjun Chen, Ganghua Zhang, Yuxing Zhu, Anshan Wu, Jianing Fang, Zhijing Yin, Haotian Chen, Ke Cao · 发表于：Cancer Cell International · 年份：2024 · DOI：10.1186/s12935-024-03387-1 · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、Endoplasmic Reticulum Stress and Disease、Cancer Immunotherapy and Biomarkers

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. METHODS: 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. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. RESULTS: Our results suggests that 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. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy i...