Disulfidptosis-related signatures for prognostic and immunotherapy reactivity evaluation in hepatocellular carcinoma.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and a nonnegligible health concern on a worldwide scale. Disulfidptosis is a novel mode of cell death, which is mainly caused by the collapse of the actin skeleton. Although many studies have demonstrated that various types of cell death are associated with cancer treatment, the relationship between disulfidptosis and HCC has not been elucidated. METHODS: Here, we mainly applied bioinformatics methods to construct a disulfidptosis related risk model in HCC patients. Specifically, transcriptome data and clinical information were downloaded from the Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) database. A total of 45 co-expressed genes were extracted between the disulfidptosis-related genes (DRGs) and the differential expression genes (DEGs) of liver hepatocellular carcinoma (LIHC) in the TCGA database. The LIHC cohort was divided into two subgroups with different prognosis by k-mean consensus clustering and functional enrichment analysis was performed. Subsequently, three hub genes (CDCA8, SPP2 and RDH16) were screened by Cox regression and LASSO regression analysis. In addition, a risk signature was constructed and the HCC cohort was divided into high risk score and low risk score subgroups to compare the prognosis, clinical features and immune landscape between the two subgroups. Finally, the prognostic model of independent risk factors was constructed and verified. CONCLUSIONS: High DRGs-related risk score in HCC individuals predict poor prognosis and are associated with poor immunotherapy response, which indicates that risk score assessment model can be utilized to guide clinical treatment strategy.