F-box protein 43 promoter methylation as a novel biomarker for hepatitis B virus-associated hepatocellular carcinoma

Ying Zhang; Jing-Wei Wang; Xing Su; Jin-E Li; Xue-Fei Wei; Jie-Ru Yang; Shuai Gao; Yu-Chen Fan; Kai Wang

doi:10.3389/fmicb.2023.1267844

F-box protein 43 promoter methylation as a novel biomarker for hepatitis B virus-associated hepatocellular carcinoma

Front Microbiol. 2023 Nov 2:14:1267844. doi: 10.3389/fmicb.2023.1267844. eCollection 2023.

Authors

Ying Zhang¹, Jing-Wei Wang², Xing Su¹, Jin-E Li¹, Xue-Fei Wei¹, Jie-Ru Yang¹, Shuai Gao^{1

3}, Yu-Chen Fan^{1

3}, Kai Wang^{1

2

3}

Affiliations

¹ Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
² Department of Hepatology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, China.
³ Hepatology Institute of Shandong University, Shandong University, Jinan, China.

Abstract

Background: Hepatocellular carcinoma (HCC) has a high prevalence and poor prognosis worldwide. Therefore, it is urgent to find effective and timely diagnostic markers. The objective of this study was to evaluate the diagnostic value of F-box protein 43 promoter methylation in peripheral blood mononuclear cells (PBMCs) for HCC.

Method: A total of 247 participants were included in this study, comprising individuals with 123 hepatitis B virus-associated HCC, 79 chronic hepatitis B, and 45 healthy controls. F-box protein 43 methylation and mRNA levels in PBMCs were detected by MethyLight and quantitative real-time PCR.

Result: F-box protein 43 promoter methylation levels were significantly lower in HCC PBMCs than the chronic hepatitis B (P < 0.001) and healthy control PBMCs (P < 0.001). Relative mRNA expression levels of F-box protein 43 in HCC PBMCs were significantly higher than those in chronic hepatitis B (P < 0.001) and healthy control PBMCs (P < 0.001). Receiver operating characteristic analysis of F-box protein 43 promoter methylation levels yielded an area under curve (AUC) of 0.793 with 76.42% sensitivity and 68.35% specificity when differentiating HCC from chronic hepatitis. These values for the F-box protein 43 promoter methylation level were superior to those of the alpha-fetoprotein serum (AFP) level (AUC: 0.780, sensitivity: 47.97%, and specificity: 96.20%), with increments in values for the combination of F-box protein 43 promoter methylation AFP levels (AUC: 0.888, sensitivity: 76.42%, and specificity: 86.08%).

Conclusion: Hypomethylation of the F-box protein 43 promoter in PBMCs is a promising biochemical marker for HBV-associated HCC.

Keywords: DNA methylation; FBXO43; MethyLight; diagnosis; hepatitis B virus-associated hepatocellular carcinoma.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Key Research and Development Program of China (2021YFC2301801), the National Natural Science Foundation of China (82272313), and the Natural Science Foundation of Shandong Province (grant number: ZR2022MH006).