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).

中文翻译：

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预测上皮性卵巢癌生存不良的UBE2T表达增加：基于UBE2s，临床样本和GEO数据库的综合分析

在各种恶性肿瘤的微环境中均已报道了泛素结合酶E2（UBE2），但它们与卵巢癌（OC）的相关性仍然难以捉摸。这项研究旨在通过Oncomine，基因表达谱分析互动分析（GEPIA），Kaplan-Meier绘图仪，cBioPortal和系统分析系统分析OC中UBE2基因家族的12个成员的表达模式，预后价值，遗传变异和生物学功能。分别是检索相互作用基因/蛋白质（STRING）数据库的搜索工具。我们发现UBE2C，UBE2N，UBE2S和UBE2T的mRNA水平与正常卵巢组织相比，OC中的蛋白显着上调。在患有浆液性卵巢癌（SOC）的患者中，UBE2A，UBE2B，UBE2C，UBE2G，UBE2R2和UBE2T的上调与总体生存期差有关。此外，UBE2A，UBE2N，UBE2R2和UBE2T的上调和UBE2G的下调与不良的无进展生存期相关。UBE2T与OC具有很强的相关性，因此需要进一步检查。我们发现UBE2T在上皮性卵巢癌（EOC）中具有很高的诊断准确性（接收器工作特征曲线下的面积= 0.969）。免疫组织化学分析和基因表达综合（GEO）数据库显示，与边缘肿瘤，良性肿瘤和正常卵巢组织相比，EOC中的UBE2T明显上调，其高表达与不良预后相关。Cox模型表明，UBE2T上调是影响EOC和SOC预后的独立危险因素。此外，UBE2T与特定的免疫细胞有关，并且主要参与细胞周期相关事件。基因组分析表明TP53和TTN突变与UBE2T表达式。基因拷贝数扩增和甲基化不足可能是导致OC中UBE2T上调的原因。总之，UBE2家族成员可能在OC的发展中发挥作用。具体而言，UBE2T可以作为该疾病的新的预后标志物和治疗靶标。（IRB批准书编号2020PS533K）。