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

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

NA HU,¹ XIAO-PENG FAN,^1,2 YU-CHEN FAN,^1,2 LONG-YAN CHEN,^1,2 CHEN-YANG QIAO,¹ LI-YAN HAN^1,2 AND KAI WANG^1,2

¹Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
2 Institute of Hepatology, Shandong University, Jinan, Shandong, P.R. China

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 ubiquitin-conjugating 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 asignificantly 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.

keywords —— hepatocellular carcinoma; methylation; MSP; serum biomarker; UBE2Q1

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Tohoku J. Exp. Med., 2017, 242, 93-100

Correspondence: Kai Wang, M.D., Ph.D., Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong Province 250012, China.

e-mail: wangdoc876@126.com or wangdoc2010@163.com