Increased Expression of UBE2T Predicting Poor Survival of Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples And the GEO Database

Abstract

Background：Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive. Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited the greatest correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C, UBE2N, UBE2S, and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A, UBE2B, UBE2C, UBE2G, and UBE2T upregulation and UBE2R2 downregulation were associated with poor overall survival. Moreover, UBE2A, UBE2N, and UBE2T upregulation and UBE2G and UBE2R2 downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors 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 ovarian cancer (hazard ratio: 4.095, P=0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and 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 ovarian cancer. Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

UBE2T regulates epithelial–mesenchymal transition through the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer

“…However, the role of UBE2T in ovarian cancer has not been specifically reported. Based on bioinformatic analysis, Zou et al reported that UBE2T might play a role in the occurrence and development of ovarian cancer [33]; however, the specific mechanism involved in this process has not been investigated.…”

Diverse roles of UBE2T in cancer (Review)

“…Moreover, UBE2T was closely associated to specific immune cells, which were mainly involved in cell cycle-related events, and in Titin and p53 mutations. UBE2T copy number amplification and hypomethylation may be responsible for its upregulation in OV (57). UBE2T overexpression of contributed to the proliferation and metastasis of cervical cancer cells, and UBE2T-overexpressing cervical cancer cells exhibited enhanced self-renewal ability.…”

“…UBE2T overexpression promoted cell proliferation, which was inhibited by UBE2T knockdown. Recently, research has focused on the function of UBE2T in tumorigenesis and tumor progression (57). Previous studies on UBE2T included BrC, bladder cancer (BC), cervical cancer, cholangiocarcinoma, colorectal cancer (CRC), esophageal cancer, lung cancer, hepatocellular carcinoma (HCC/liver HCC), melanoma, nasopharyngeal carcinoma, osteosarcoma, ovarian cancer and pancreatic cancer (PCA).…”