Disulfidptosis-related prognostic model based on multiomics and the significance of IL1B in ovarian cancer

Abstract

Abstract Background Ovarian cancer (OC) is a significant health concern for women due to high mortality rates. Disulfidptosis is a newly discovered mechanism of caspase-driven programmed cell death that may be significant for cancer treatment. Methods The bulk RNA-seq data of 378 OC patients in TCGA-OV cohort and 174 patients in GSE53963 dataset, and the single-cell RNA-seq data of 4 high-grade SOC patients in GSE154600 were retrieved. The disulfidptosis score was calculated by gene set enrichment analysis (GSEA) based on the disulfidptosis pathway using the AddModuleScore function of the Seurat package. The patients were divided into the two groups based on the risk score, which were then compared using consensus clustering, WCGNA and functional enrichment analysis. LASSO regression and cox regression were performed to construct a risk score model. Immune cell infiltration was analyzed by xcell and ssGSEA. IL1B was knocked down in OC cell lines, and routine in vitro and in vivo functional assays were performed. Results We identified 6 cell clusters in OC and divided them on the basis of the disulfidptosis score. The two groups showed distinct functional difference. Likewise, OC patients divided into disulfidptosis score-related groups showed significant difference in survival status, along with enrichment of immune response-related pathways. Seven prognostic genes related to disulfidptosis were screened by Cox regression and LASSO regression analyses, and the risk score was calculated. The high-risk score was associated with significantly worse survival in the validation cohort. In addition, the abundance of activated T cells was higher, and that of Tregs and MDSCs were lower in the low-risk group compared to the high-risk group. Finally, IL1B silencing inhibited the proliferation, migration, and invasion of OC cells in vitro and in vivo. Conclusion The disulfidptosis-based risk model can accurately predict the prognosis and immune characteristics of OC patients. IL1B functions as an oncogene in OC, and is a promising therapeutic target.