Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the Carcinogenesis and Progression of Hepatocellular Carcinoma

Abstract

Background The purpose of this study was to screen and identify key genes in the occurrence and development of hepatocellular carcinoma (HCC) based on bioinformatics analysis. Material/Methods Three Gene Expression Omnibus (GEO) series (GSE) – GSE121248, GSE87630, and GSE84598 – were downloaded from the GEO database. GEO2R was used to screen different genes and a Venn diagram was drawn to screen coexpressed differentially expressed genes (DEGs). Coexpressed DEGs were obtained by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, a protein-protein interaction network diagram was produced by Cytoscape, and module genes were calculated by the Molecular Complex Detection Cytoscape plug-in. Finally, overall survival, progression-free survival, and relapse-free survival analysis of the key genes selected were performed using the online Kaplan-Meier plotter. For the target genes, the online network UCSC Cancer Genome Browser was used to analyze the gene expression profiles of the grade and vascular invasion of HCC. Results A total of 296 coexpressed DEGs were obtained from the 3 GSEs and 12 key genes were obtained from the modular analysis. Survival analysis showed that the upregulated genes UBE2T and FBLN5 were involved in the poor prognosis of HCC. Furthermore, the expression of UBE2T was significantly related to the grade and vascular invasion of HCC. Conclusions The expression of the UBE2T gene was significantly upregulated in HCC tissue compared to in normal liver tissue. UBE2T may be a new marker for the diagnosis and subsequent therapy of HCC.

Diverse roles of UBE2T in cancer (Review)

“…The level of UBE2T was significantly higher in stages II and III than in stage I (30). In addition, it was confirmed to have notable advantages with HCC grade, HCC satellite lesions and vascular invasion (63). miR-543 directly targeted UBE2T, which was downregulated in HCC.…”

“…Overexpression of UBE2T was negatively correlated with prognosis and overall survival (OS) time, while it was positively correlated with pathological grade and TNM stage of HCC progression, which showed higher expression at all four stages compared with that of non-cancer control samples (8,30,63). The level of UBE2T was significantly higher in stages II and III than in stage I (30).…”

Screening of Hub Genes Associated with Lung Adenocarcinoma by Integrated Bioinformatic Analysis

“…In [70,71] and also lung cancer [72]. A study showed that UBE2T promoted proliferation, migration, invasion, and radiation resistance in vitro and in vivo by accelerating the G2/M transition and inhibiting apoptosis and in mechanism, UBE2T promotes epithelial-mesenchymal transition via ubiquitination-mediated FOXO1 degradation and Wnt/β-catenin signaling pathway activation in NSCLC [72,73].…”

Ubiquitin‑conjugating enzymes as potential biomarkers and therapeutic targets for digestive system cancers (Review)

“…MiR-543 may also regulate UBE2T ubiquitination and degrades p53 protein. MiR-1305 is also able to target it to inhibit the Akt signaling pathway and inhibit the self-renewal and tumorigenesis of liver cancer stem cells (95)(96)(97)(98)(99)(100). UBE2T is the sumoylation target of SUMO-specific peptidase 1, which mediates its carcinogenic effects (101).…”