Increased Expression of <i>UBE2T</i> Predicting Poor Survival of Epithelial Ovarian Cancer: Based on Comprehensive Analysis of <i>UBE2s</i> , Clinical Samples, and the GEO Database

Abstract

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 <i>UBE2</i> 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 <i>UBE2C</i>, <i>UBE2N</i>, <i>UBE2S</i>, and <i>UBE2T</i> were significantly upregulated in OC compared with those in normal ovarian tissue. In patients with serous ovarian cancer (SOC), <i>UBE2A</i>, <i>UBE2B</i>, <i>UBE2C</i>, <i>UBE2G</i>, <i>UBE2R2</i>, and <i>UBE2T</i> upregulation were associated with poor overall survival. Moreover, <i>UBE2A</i>, <i>UBE2N</i>, <i>UBE2R2</i>, and <i>UBE2T</i> upregulation and <i>UBE2G</i> downregulation were associated with poor progression-free survival. <i>UBE2T</i> exhibited a strong correlation with OC and was thus further examined. We found that <i>UBE2T</i> 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 <i>UBE2T</i> 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 <i>UBE2T</i> upregulation was an independent risk factor affecting the prognosis of EOC and SOC. Furthermore, <i>UBE2T</i> was associated with specific immune cells and was mainly involved in cell cycle-related events. Genomic analysis showed that <i>TP53</i> and <i>TTN</i> mutations were associated with <i>UBE2T</i> expression. Gene copy number amplification and hypomethylation may be responsible for <i>UBE2T</i> upregulation in OC. In conclusion, <i>UBE2</i> family members may play a role in the development of OC. Specifically, <i>UBE2T</i> could serve as a new prognostic marker and therapeutic target for this disease. (IRB Approval No. 2020PS533K).