Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer (OC) remains elusive. This study aimed to systematically analyze the expression patterns, prognostic value, genetic variation, and biological functions of 12 members of the UBE2 gene family in OC through the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases, respectively. We found that the mRNA levels of UBE2C, UBE2N, UBE2S, and UBE2T were significantly upregulated in OC compared with those in normal ovarian tissue. In patients with serous ovarian cancer (SOC), UBE2A, UBE2B, UBE2C, UBE2G, UBE2R2, and UBE2T upregulation were associated with poor overall survival. Moreover, UBE2A, UBE2N, UBE2R2, and UBE2T upregulation and UBE2G downregulation were associated with poor progression-free survival. UBE2T exhibited a strong correlation with OC and was thus further examined. We found that UBE2T has a high diagnostic accuracy (area under the receiver operating characteristic curve = 0.969) in epithelial ovarian cancer (EOC). Immunohistochemical assays and the Gene Expression Omnibus (GEO) database revealed that UBE2T was significantly upregulated in EOC compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of EOC and SOC. Furthermore, UBE2T was associated with specific immune cells and was mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in OC. In conclusion, UBE2 family members may play a role in the development of OC. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease. (IRB Approval No. 2020PS533K).

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