Tohoku J. Exp. Med., 2020 December, 252(4)

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

LA-MEI CHEN,¹ LIN XIANG,¹ WEI-JUAN SUN,¹ YU-JIA ZHAI,¹ SHUAI GAO,^1,2 YU-CHEN FAN^1,2,3 and KAI WANG^1,2,3

¹Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
²Institute of Hepatology, Shandong University, Jinan, Shandong, China
³Shenzhen Research Institute of Shandong University, Shenzhen, Guangdong, China

Wnt1-inducible signaling pathway protein 1 (WISP1) regulates cell proliferation, differentiation, adhesion, migration and survival. Abnormal WISP1 expression is associated with the carcinogenesis of hepatocellular carcinoma (HCC). Aberrant DNA methylation is one of the major epigenetic alterations in HCC. However, the methylation status of the WISP1 promoter is still unclear. We therefore aimed to determine the methylation status of the WISP1 promoter and evaluate its clinical value in HCC. The study enrolled 251 participants, including 123 participants with HCC, 90 participants with chronic hepatitis B (CHB) and 38 healthy controls (HCs). WISP1 methylation status, mRNA levels and plasma soluble WISP1 were detected by methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. We found that the methylation frequency of WISP1 in patients with HCC was significantly lower than that in patients with CHB and HCs, while the relative expression levels of WISP1 mRNA were markedly higher in patients with HCC than in patients with CHB and HCs. Furthermore, the plasma soluble WISP1 in patients with HCC was obviously lower than in that in patients with CHB and HCs. Alpha-fetoprotein (AFP) is a widely recognized biomarker to diagnose HCC which lacks enough sensitivity and specificity. WISP1 promoter methylation status combined with AFP significantly improved the diagnostic ability in discriminating HCC from CHB compared with AFP or WISP1 methylation status alone. In conclusion, hypomethylation of the WISP1 gene promoter may serve as a noninvasive biomarker for detecting HBV-associated HCC.

Keywords —— biomarker; DNA methylation; hepatocellular carcinoma; methylation-specific polymerase chain reaction; Wnt1-inducible signaling pathway protein 1

© 2020 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2020 252, 297-307.

Correspondence: Kai Wang, Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, 107# Wenhuaxi Road, Jinan, Shandong 250012, China.

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