鉴定血清β-连环蛋白作为HBV相关肝病患者的生物标志物

StephenW

Identification of serum β-catenin as a biomarker in patients with HBV-related liver diseases

    Liang Duan†, Qianfan Yang†, Jun Yang, Qin Hu, Bo Wang, Pu Li and Weixian ChenEmail author

†Contributed equally
Journal of Translational Medicine201816:265

https://doi.org/10.1186/s12967-018-1645-x

©  The Author(s) 2018

    Received: 2 August 2018Accepted: 25 September 2018Published: 29 September 2018

Abstract
Background

Substantial evidence indicates that β-catenin is a pivotal regulator that contributes to the initiation and development of various types of diseases. Recently, β-catenin can be detected in human serum and also reported to be correlated with several disease progression in a little research. However, very little is known about the relationship between serum β-catenin and HBV-related liver disease.
Methods

Serum levels of β-catenin, from 77 patients with chronic hepatitis B (CHB), 63 patients with hepatitis B associated liver cirrhosis (HBLC), 61 patients with hepatocellular carcinoma (HCC), 41 healthy HBV carriers (HHCs) and 78 healthy controls (HCs) were measured by ELISA. Correlations of serum β-catenin with viral replication and liver necroinflammation parameters were analyzed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum β-catenin to grade different stages of HBV-related disorders. Human hepatic cell line L02 was transfected with a HBV plasmid, and β-catenin levels and the underlying mechanism were analyzed.
Results

Chronic hepatitis B and HBLC patients but not HHC or HCC showed significantly higher serum β-catenin levels than HCs. β-catenin levels were not correlated with HBV DNA levels but were correlated with necroinflammation parameters. HBV-infected cell model showed elevated levels of phosphorylation at Ser473 in Akt (p-Akt), phosphorylation at Ser9 in GSK3β (p-GSK3β) and β-catenin, all of which was blocked by treatment with Akt inhibitor LY294002. Additionally, ROC analysis of β-catenin for discriminating patients with CHB from HHCs, which yielded an AUC of 0.71 (cutoff value, 42 pg/mL; 95% CI 0.61–0.81) with 64.93% sensitivity, 73.17% specificity and 69.05% accuracy. ROC analysis of β-catenin for discriminating patients with HCC from chronic HBV infection mainly including CHB and HBLC, which yielded an AUC of 0.75 (cutoff value, 42 pg/mL; 95% CI 0.67–0.83) with 66.43% sensitivity, 75.41% specificity and 70.92% accuracy.
Conclusions

HBV infection enhances β-catenin expression by activating Akt/GSK3β signaling. Serum β-catenin levels are correlated with necroinflammation parameters but not with viral load. Serum β-catenin has potential to discriminate the phase of HBV-related disorders, particularly predicts the patients with CHB from HHCs and also predicting HCC form chronic HBV infection.
Keywords

    Hepatitis B virus
    β-Catenin
    Chronic hepatitis
    Liver disease

StephenW

鉴定血清β-连环蛋白作为HBV相关肝病患者的生物标志物

    梁端†，杨帆凡†，杨军，秦虎，王波，李璞，陈伟贤，电子邮件作者

†同等贡献
Journal of Translational Medicine201816：265

https://doi.org/10.1186/s12967-018-1645-x

©作者2018

    收稿日期：2018年8月2日接受日期：2018年9月25日出版日期：2018年9月29日

抽象
背景

大量证据表明，β-连环蛋白是一种关键的调节因子，有助于各种疾病的发生和发展。最近，β-连环蛋白可以在人血清中检测到，并且据报道在一些研究中与几种疾病进展相关。然而，关于血清β-连环蛋白和HBV相关肝病之间的关系知之甚少。
方法

77例慢性乙型肝炎（CHB）患者，63例乙型肝炎肝硬化（HBLC）患者，61例肝细胞癌（HCC）患者，41例健康HBV携带者（HHCs）和78例健康对照者血清β-catenin水平通过ELISA测量（HC）。分析血清β-连环蛋白与病毒复制和肝脏坏死性炎症参数的相关性。接受者操作特征（ROC）曲线用于评估血清β-连环蛋白的鉴别能力，以评定HBV相关疾病的不同阶段。用HBV质粒转染人肝细胞系L02，并分析β-连环蛋白水平和潜在的机制。
结果

慢性乙型肝炎和HBLC患者但不是HHC或HCC显示血清β-连环蛋白水平显着高于HCs。 β-连环蛋白水平与HBV DNA水平无关，但与坏死性炎症参数相关。 HBV感染的细胞模型显示Akt（p-Akt）中Ser473的磷酸化水平升高，GSK3β（p-GSK3β）和β-连环蛋白中Ser9的磷酸化，所有这些都被Akt抑制剂LY294002处理阻断。此外，用于区分CHH患者的β-连环蛋白的ROC分析，其产生的AUC为0.71（截止值，42 pg / mL; 95％CI 0.61-0.81），灵敏度为64.93％，特异性为73.17％，准确度为69.05％ 。用于鉴别慢性HBV感染的HCC患者的β-catenin的ROC分析主要包括CHB和HBLC，其产生的AUC为0.75（截断值，42 pg / mL; 95％CI 0.67-0.83），敏感性为66.43％，75.41％特异性和70.92％的准确性。
结论

HBV感染通过激活Akt /GSK3β信号传导增强β-连环蛋白的表达。血清β-连环蛋白水平与坏死性炎症参数相关，但与病毒载量无关。血清β-连环蛋白具有区分HBV相关疾病阶段的潜力，特别是预测来自HHC的CHB患者并且还预测HCC形成慢性HBV感染。
关键词

    乙型肝炎病毒
    β-连环蛋白
    慢性肝炎
    肝病

StephenW

https://translational-medicine.b ... 6/s12967-018-1645-x