Multi-omics analysis defines a cuproptosis-related prognostic model for ovarian cancer: Implication of WASF2 in cuproptosis resistance
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Ovarian cancer (OVC) is one of the deadliest and most aggressive tumors in women, with an increasing incidence in recent years. Cuproptosis, a newly discovered type of programmed cell death, is caused by intracellular copper-mediated lipoylated protein aggregation and proteotoxic stress. However, the role of cuproptosis-related features in OVC remains elusive. The single-cell sequencing data from GSE154600 and bulk transcriptome data of 378 OVC patients from TCGA database. The RNA-seq and clinical data of 379 OVC patients in GSE140082 and 173 OV patients in GSE53963. The PROGENy score was calculated to assess tumor-associated pathways. Based on gene set enrichment analysis (GSEA) of the cuproptosis pathway, the single cells were divided into the cuproptosis Six major cell populations was identified, including fibroblast, T cell, myeloid, epithelial cell, endothelial cell, and B cell populations. The PROGENy score which revealed significant activation of the PI3K pathway in T and B cells, and activation of the TGF-β pathway in endothelial cells and fibroblasts. TIMM8B, COX8A, SSR4, HIGD2A, WASF2, PRDX5 and CLDN4 were selected to construct a prognostic model from the identified 47 prognosis-related genes. Furthermore, the cuproptosis A clinically significant cuproptosis-related prognostic model was identified which can accurately predict the prognosis and immune characteristics of OVC patients. WASF2, one of the cuproptosis-related gene in the risk model, promotes the proliferation and platinum resistance of OVC cells, and leads poor prognosis.