Hypomethylated Ubiquitin-Conjugating Enzyme2 Q1 (UBE2Q1) Gene Promoter in the Serum Is a Promising Biomarker for Hepatitis B Virus-Associated Hepatocellular Carcinoma

Abstract

Aberrant DNA methylation, which can be detected in circulating cell-free DNA (cfDNA), is one of the major epigenetic alterations in hepatocellular carcinoma (HCC). UBE2Q1, a putative member of the ubiquitinconjugating enzyme family, might play substantial roles in tumorigenesis. However, the methylation status of the UBE2Q1 gene in HCC remains unknown. We aimed to determine the methylation status of the UBE2Q1 gene promoter and to evaluate its potential clinical significance for HCC detection. The methylation-specific polymerase chain reaction (MSP) assay was used to detect the UBE2Q1 gene methylation status in serum samples from 80 patients with hepatitis B virus (HBV)-related HCC, 40 patients with liver cirrhosis (LC), 40 patients with chronic hepatitis B (CHB), and 20 healthy controls (HCs). Significantly lower methylation frequencies were detected in HCC patients (33.75%) compared with LC patients (55.00%, p = 0.026) and CHB patients (60.00%, p = 0.006) and HCs (65.00%, p = 0.011). Hypomethylation of the UBE2Q1 gene was negatively associated with the tumor node metastasis stage (r s = −0.30, p = 0.008). The UBE2Q1 gene methylation status combined with alpha fetoprotein using cut-off points of 20, 200 and 400 ng/ml showed sensitivity and specificity values of 58.8% and 75.0%, 53.8% and 87.5%, and 37.5% and 88.7%, respectively, and yielded a significantly increased area under the ROC curve (0.720, 0.760 and 0.694, respectively) for discriminating HCC from LC and CHB. Our study results suggest that hypomethylation of the UBE2Q1 gene promoter is a potential biomarker for detecting HBV-associated HCC.

Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review

“…57,59,61,69,73,[77][78][79]84,[86][87][88][89][90][91]94 Ten studies compared scores incorporating various components of cfDNA (ranging from amount of cfDNA to methylation of or mutation in specific genes) and AFP, and found that the combination had superior test characteristics than AFP level alone. 60,[64][65][66][67][68]74,76,83,85,93 Thirteen of 14 studies comparing the combination of cfDNA and AFP with cfDNA alone found that the combination had superior sensitivity and/or specificity, 60,[64][65][66][67][68]70,75,76,83,85,89,93 however, the incremental value of AFP was not observed in a recent large study in the United States. 74 Extracellular vesicles.…”

Current status of ctDNA in precision oncology for hepatocellular carcinoma

“…It is reported that ctDNA assay of the hypomethylation level nearby HBV integration sites can serve as an early detection tool for HCC [103]. Other genes, such as CTCFL promoters and UBE2Q1, the hypomethylation status of which in ctDNA are also believed to be relevant to the diagnostic and monitoring period for HCC patients [104,105].…”

Diagnostic Value of the Hypomethylation of the <i>WISP1</i> Promoter in Patients with Hepatocellular Carcinoma Associated with Hepatitis B Virus

“…Cancer develops through the accumulation of genetic and epigenetic aberrations, and epigenetic changes are strongly associated with the development of HCC. As reported, many genes such as ADRAIA, ACADS, UBE2Q1, and ZCCH13 have been found to have aberrant methylation status in HCC (Hu et al 2017;Chen et al 2019;Li et al 2019;Chen et al 2020). Abnormal methylation of genes may be promising biomarkers to timely and accurately distinguish patients with HBV-associated HCC from patients with CHB.…”