Identification of serum β-catenin as a biomarker in patients with HBV-related liver diseases.
Identification of serum β-catenin as a biomarker in patients with HBV-related liver diseases.
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鉴定血清 β-连环蛋白作为 HBV 相关肝病患者的生物标志物。
DOI：
10.1186/s12967-018-1645-x
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发表时间：
2018-09-29
影响因子：
7.4
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Duan L;Yang Q;Yang J;Hu Q;Wang B;Li P;Chen W
大量证据表明β-连环蛋白是促进各类疾病发生和发展的关键调节因子。最近，β-连环蛋白可以在人血清中检测到，并且在一些研究中还报道其与多种疾病进展相关。然而，人们对血清β-连环蛋白与HBV相关肝病之间的关系知之甚少。采用 ELISA 方法检测 77 例慢性乙型肝炎 (CHB) 患者、63 例乙型肝炎相关性肝硬化 (HBLC) 患者、61 例肝细胞癌 (HCC) 患者、41 例健康 HBV 携带者 (HHC) 和 78 例健康对照 (HC) 的血清 β-连环蛋白水平。分析血清β-连环蛋白与病毒复制和肝脏坏死炎症参数的相关性。受试者工作特征 (ROC) 曲线用于评估血清 β-连环蛋白对 HBV 相关疾病不同阶段进行分级的区分能力。用HBV质粒转染人肝细胞系L02，并分析β-catenin水平及其潜在机制。慢性乙型肝炎和 HBLC 患者（而非 HHC 或 HCC）的血清 β-连环蛋白水平显着高于 HC 患者。 β-连环蛋白水平与 HBV DNA 水平不相关，但与坏死性炎症参数相关。 HBV 感染细胞模型显示 Akt (p-Akt) 中 Ser473 的磷酸化水平升高、GSK3β (p-GSK3β) 和 β-catenin 中 Ser9 的磷酸化水平升高，所有这些都被 Akt 抑制剂 LY294002 治疗所阻断。此外，用于区分 CHB 患者和 HHC 的 β-连环蛋白 ROC 分析得出的 AUC 为 0.71（截止值，42 pg/mL；95% CI 0.61–0.81），敏感性为 64.93%，特异性为 73.17%，准确性为 69.05%。 β-连环蛋白的 ROC 分析用于区分 HCC 患者与慢性 HBV 感染（主要包括 CHB 和 HBLC），其 AUC 为 0.75（截止值，42 pg/mL；95% CI 0.67–0.83），敏感性为 66.43%，特异性为 75.41%，准确性为 70.92%。 HBV 感染通过激活 Akt/GSK3β 信号传导增强 β-catenin 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-连环蛋白有可能区分 HBV 相关疾病的阶段，特别是预测 HHC 中的 CHB 患者，以及预测慢性 HBV 感染中的 HCC。
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. 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. 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. 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.
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作者：
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