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UBE2Q1 启动子异常甲基化与慢加急性乙型肝炎肝衰竭预后不良相关。

Aberrant methylation of UBE2Q1 promoter is associated with poor prognosis of acute-on-chronic hepatitis B pre-liver failure.

机构信息

Department of Internal Medicine of Shandong Medical College.

Department of Gastroenterology, Affiliated Hospital of Shandong Medical College.

出版信息

Medicine (Baltimore). 2021 May 28;100(21):e26066. doi: 10.1097/MD.0000000000026066.

Abstract

Acute-on-chronic hepatitis B liver failure (ACHBLF) is one severe liver disease with rapid progression and high mortality. Identification of specific markers for the prediction of ACHBLF has important clinical significance. We explored the feasibility of UBE2Q1 gene promoter methylation as an early prediction and prognosis biomarker of ACHBLF.UBE2Q1 promoter methylation frequency was detected in 60 patients with acute-on-chronic hepatitis B pre-liver failure (Pre-ACHBLF), 40 patients with chronic hepatitis B and 20 cases of healthy control (HC). The UBE2Q1 mRNA was detected by quantitative real-time polymerase chain reaction.The methylation frequency of the UBE2Q1 promoter in pre-ACHBLF patients was 38.33%, which was significantly lower than that in chronic hepatitis B patients (60.00%) and HCs (65.00%). The UBE2Q1 mRNA expression in pre-ACHBLF patients with UBE1Q1 non-methylation was significantly higher than that in patients with UBE1Q1 promoter methylation. Further analysis showed that hypomethylation of the UBE2Q1 promoter was positively correlated with total bilirubin and international normalized ratio levels in patients with pre-ACHBLF, but negatively correlated with PTA level. COX multivariate analysis showed that the model for end-stage liver disease score and UBE2Q1 promoter hypomethylation status were potential early warning factors that can predict the progression of pre-ACHBLF to ACHBLF. The sensitivity and specificity of UBE2Q1 promoter methylation status combined with the model for end-stage liver disease score for early diagnosis of ACHBLF were 92.9% and 75.0%, respectively. The area under the receiver-operating characteristic curve was 0.895.The hypomethylation of UBE2Q1 promoter is associated with severity of Pre-ACHBLF, which could serve as a potential prognostic biomarker for pre-ACHBLF.

摘要

慢加急性乙型肝炎肝衰竭(ACHBLF)是一种进展迅速、死亡率高的严重肝脏疾病。鉴定用于预测 ACHBLF 的特定标志物具有重要的临床意义。我们探讨了 UBE2Q1 基因启动子甲基化作为 ACHBLF 早期预测和预后生物标志物的可行性。检测 60 例乙型肝炎慢加急性肝衰竭前期(Pre-ACHBLF)患者、40 例慢性乙型肝炎患者和 20 例健康对照者(HC)中 UBE2Q1 基因启动子甲基化频率。采用实时荧光定量聚合酶链反应检测 UBE2Q1mRNA。Pre-ACHBLF 患者 UBE2Q1 启动子甲基化频率为 38.33%,明显低于慢性乙型肝炎患者(60.00%)和 HC(65.00%)。UBE2Q1 启动子非甲基化的 Pre-ACHBLF 患者 UBE2Q1mRNA 表达明显高于 UBE2Q1 启动子甲基化患者。进一步分析显示,Pre-ACHBLF 患者 UBE2Q1 启动子低甲基化与总胆红素和国际标准化比值水平呈正相关,与 PTA 水平呈负相关。COX 多因素分析显示,终末期肝病模型评分和 UBE2Q1 启动子低甲基化状态是预测 Pre-ACHBLF 进展为 ACHBLF 的潜在预警因素。UBE2Q1 启动子甲基化状态联合终末期肝病模型评分对 ACHBLF 的早期诊断的敏感性和特异性分别为 92.9%和 75.0%,ROC 曲线下面积为 0.895。UBE2Q1 启动子低甲基化与 Pre-ACHBLF 的严重程度相关,可能成为 Pre-ACHBLF 的潜在预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a3/8154380/52322aeb09ce/medi-100-e26066-g001.jpg

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