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循环 microRNAs 作为慢性丙型肝炎(基因型 4)埃及患者肝病进展的预测生物标志物。

Circulating microRNAs as predictive biomarkers for liver disease progression of chronic hepatitis C (genotype-4) Egyptian patients.

机构信息

Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt.

Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.

出版信息

J Med Virol. 2019 Jan;91(1):93-101. doi: 10.1002/jmv.25294. Epub 2018 Sep 24.

Abstract

Egypt is one of the highest prevalence rates of hepatitis C virus (HCV) infection worldwide. HCV is among major reasons for chronic liver diseases. MicroRNA (miRNAs), small noncoding regulatory molecules play a key role in the pathogenesis of liver. Circulating miRNAs represent potential noninvasive biomarkers for diagnosis and monitoring patients with liver diseases progression. To investigate the potential role of circulating miRNAs for surveillance of liver disease progression, we assessed the expression of 20 liver-related miRNAs in sera of 47 chronic hepatitis C Egyptian patients compared with 25 controls using quantitative reverse-transcription polymerase chain reaction assay. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve. The correlations between their levels and the clinicopathological features were assessed. Fourteen miRNAs showed upregulation and six miRNAs showed downregulation. ROC curve analyses revealed that the explored miRNAs could serve as valuable biomarkers for chronic hepatitis with an area under the curve ranged from 0.708 (95% confidence interval [95% CI], 0.587 to 0.829; P = 0.004) for miR-199 up to 0.974 (95% CI, 0.943 to 1.00; P < 0.001) for miR-23b. The expression level of miR-21 demonstrated significant correlation with age, liver enzymes, ALT/AST, and α-fetoprotein level. AST level was directly correlated with miR-122, while an inversely correlated with miR-23b. Fibrosis and steatosis stages possessed positive correlation with miR-199 expression and negative correlation with miR-27a and miR-93. In conclusion, miR-23b and miR-106 might be a useful biomarker for chronic hepatitis C (CHC). MiR-27a, miR-93, and miR-199 might have a potential role in the progression of liver diseases. Unravel the role of these miRNAs in CHC patients might lead to precise prognosis and management.

摘要

埃及是丙型肝炎病毒 (HCV) 感染率最高的国家之一。HCV 是导致慢性肝病的主要原因之一。微小 RNA (miRNA) 是一种小型非编码调节分子,在肝脏发病机制中起着关键作用。循环 miRNA 是诊断和监测肝脏疾病进展的潜在非侵入性生物标志物。为了研究循环 miRNA 在监测肝脏疾病进展中的潜在作用,我们使用定量逆转录聚合酶链反应 (qRT-PCR) 检测了 47 例埃及慢性丙型肝炎患者和 25 例对照血清中 20 种肝脏相关 miRNA 的表达。使用受试者工作特征 (ROC) 曲线评估了敏感性和特异性。评估了它们的水平与临床病理特征之间的相关性。14 种 miRNA 上调,6 种 miRNA 下调。ROC 曲线分析表明,所研究的 miRNA 可作为慢性肝炎的有价值的生物标志物,曲线下面积范围从 miR-199 的 0.708(95%置信区间 [95%CI],0.587 至 0.829;P=0.004)到 miR-23b 的 0.974(95%CI,0.943 至 1.00;P<0.001)。miR-21 的表达水平与年龄、肝酶、ALT/AST 和甲胎蛋白水平显著相关。AST 水平与 miR-122 呈正相关,与 miR-23b 呈负相关。纤维化和脂肪变性阶段与 miR-199 的表达呈正相关,与 miR-27a 和 miR-93 呈负相关。总之,miR-23b 和 miR-106 可能是慢性丙型肝炎 (CHC) 的有用生物标志物。miR-27a、miR-93 和 miR-199 可能在肝脏疾病的进展中具有潜在作用。阐明这些 miRNA 在 CHC 患者中的作用可能有助于精确预后和管理。

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