全基因组甲基化在急性-慢性乙型肝炎肝功能衰竭的预后值
Haiming Li1, Shuai Gao1, Jieru Yang1
1Department of Hepatology, Shandong University Qilu Hospital, Jinan 250012, China.
Pathology, research and practice
|March 7, 2024
概括
全球基因组甲基化水平在急性至慢性乙型肝炎肝衰竭 (ACHBLF) 患者中明显高于慢性乙型肝炎患者. 这种表观遗传标记显示出作为ACHBLF严重程度的优越预后指标的希望.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 生物标志物发现发现
背景情况:
- 基因组甲基化模式在乙型肝炎的不同阶段不同,包括前急性至慢性肝衰竭 (pre-ACHBLF),急性至慢性肝衰竭 (ACHBLF) 和慢性乙型肝炎 (CHB).
- 确定可靠的预后指标对于管理严重临床结果的ACHBLF至关重要.
研究的目的:
- 为了研究全球基因组甲基化水平和DNA甲基转移酶 (DNMT) 活性,在不同阶段的乙型肝炎肝病患者.
- 评估全球基因组甲基化作为ACHBLF预后生物标志物的潜力,将其疗效与MELD评分进行比较.
主要方法:
- 全球基因组甲基化水平在外周血液单核细胞 (PBMC) 中使用色度测试量定量.
- 通过活性试验和qRT-PCR分别评估了DNA甲基转移酶 (DNMT) 活性和DNMT和甲基-CpG结合域 (MBD) 蛋白质的基因表达.
- 采用接收器操作特征 (ROC) 曲线分析来比较全球基因组甲基化和MELD得分的预后性能.
主要成果:
- 与CHB组相比,ACHBLF组的全球基因组甲基化水平和DNMT活性显著增加 (P<0.001).
- 在ACHBLF患者中,DNMT1和MBD1的mRNA表达上调,而MBD3和MBD4与健康对照组相比表达下降.
- 全球基因组甲基化显示出更高的预测准确度 (AUC 0.950) 超过MELD得分 (AUC 0.863) 的ACHBLF预后 (P=0.0429).
结论:
- 全球基因组甲基化水平是预测急性-慢性乙型肝炎肝衰竭的严重程度和预后的有价值生物标志物.
- 表观遗传修饰,特别是全球DNA甲基化,为改善ACHBLF患者的临床管理和风险分层提供了一个有希望的途径.
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