Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, Liaoning, China.
DNA Cell Biol. 2021 Jan;40(1):36-60. doi: 10.1089/dna.2020.5823. Epub 2020 Nov 11.
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 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 , , , and were significantly upregulated in OC compared with those in normal ovarian tissue. In patients with serous ovarian cancer (SOC), , , , , , and upregulation were associated with poor overall survival. Moreover, , , , and upregulation and downregulation were associated with poor progression-free survival. exhibited a strong correlation with OC and was thus further examined. We found that 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 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 upregulation was an independent risk factor affecting the prognosis of EOC and SOC. Furthermore, was associated with specific immune cells and was mainly involved in cell cycle-related events. Genomic analysis showed that and mutations were associated with expression. Gene copy number amplification and hypomethylation may be responsible for upregulation in OC. In conclusion, family members may play a role in the development of OC. Specifically, could serve as a new prognostic marker and therapeutic target for this disease. (IRB Approval No. 2020PS533K).
泛素结合酶 E2 (UBE2) 已在各种恶性肿瘤的微环境中被报道,但它们与卵巢癌 (OC) 的相关性仍不清楚。本研究旨在通过 Oncomine、基因表达谱分析交互分析 (GEPIA)、Kaplan-Meier 绘谱器、cBioPortal 和搜索工具检索交互基因/蛋白质 (STRING) 数据库,分别系统分析 12 个基因家族成员在 OC 中的表达模式、预后价值、遗传变异和生物学功能。我们发现,与正常卵巢组织相比,OC 中 、 、 和 的 mRNA 水平显著上调。在浆液性卵巢癌 (SOC) 患者中, 、 、 、 、 和 上调与总生存期不良相关。此外, 、 、 、 和 上调和 下调与无进展生存期不良相关。 上调与 OC 具有强相关性,因此进一步进行了研究。我们发现 对上皮性卵巢癌 (EOC) 具有较高的诊断准确性 (ROC 曲线下面积 = 0.969)。免疫组织化学检测和基因表达综合数据库 (GEO) 显示,与交界性肿瘤、良性肿瘤和正常卵巢组织相比,EOC 中 显著上调,其高表达与预后不良相关。Cox 模型显示, 上调是影响 EOC 和 SOC 预后的独立危险因素。此外, 与特定免疫细胞相关,主要参与细胞周期相关事件。基因组分析表明, 和 突变与 表达相关。基因拷贝数扩增和低甲基化可能是 OC 中 上调的原因。综上所述, 家族成员可能在 OC 的发生发展中发挥作用。具体而言, 可能成为该疾病新的预后标志物和治疗靶点。(IRB 批准号:2020PS533K)。