Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma

Abstract

Abstract Epithelial ovarian carcinoma (EOC) is the most fatal among female reproductive system tumors. The immune tumor microenvironment and ubiquitin-proteasome pathway are closely related to the proliferation, invasion, and response to chemotherapy in EOC. However, their specific roles in EOC have not been fully elucidated. Therefore, we aimed to recognize potential prognostic markers and novel therapeutic targets for EOC. We constructed the ubiquitin-related signature risk model comprising HSP90AB1, FBXO9, SIGMAR1, STAT1, SH3KBP1, EPB41L2, DNAJB6, VPS18, PPM1G, AKAP12, FRK, and PYGB, specifically for patients with EOC. The high-risk model presented a worse prognosis, primarily associated with the B-cell receptor signaling pathway, ECM receptor interaction, focal adhesion, and actin cytoskeleton regulations. Analysis of the immune landscape revealed a higher abundance of B cells, M2 macrophages, neutrophil CD4 T cells, cancer-associated fibroblasts, macrophage neutrophils, and fibroblasts in the high-risk group. It also exhibited lower tumor mutation burden, mRNAsi, and EREG-mRNAsi and reduced sensitivity to other chemotherapy drugs, except dasatinib. These findings serve as a valuable indicator for personalized treatment strategies and clinical stratification in managing patients with EOC. Additionally, our study will serve as a foundation for future mechanistic research to explore the association between the ubiquitin-proteasome pathway and EOC.