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循环 miR-182 和 miR-150 作为埃及丙型肝炎病毒感染后肝硬化和肝细胞癌生物标志物的作用。

Role of circulating miR-182 and miR-150 as biomarkers for cirrhosis and hepatocellular carcinoma post HCV infection in Egyptian patients.

机构信息

Department of Clinical & Chemical Pathology, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt.

Endemic Medicine Department, Liver Unit, Cairo University Center of Hepatic Fibrosis (CUC-HF), Faculty of Medicine, Cairo University, Egypt.

出版信息

Virus Res. 2018 Aug 15;255:77-84. doi: 10.1016/j.virusres.2018.07.004. Epub 2018 Jul 9.

Abstract

In Egypt, liver diseases are exceptionally high, maintaining the highest prevalence of hepatitis C virus (HCV) worldwide, and increasing rates of hepatocellular carcinoma (HCC). Available diagnostic methods show poor performance in early diagnosis of HCC. Definite pathogenic factors contributing in the development of HCV are still lacking. MicroRNAs have been reported as promising biomarkers for cancers diagnosis and in virus-host interaction. This study was conducted to detect the role of miR-182 and miR-150 as biomarkers for development of cirrhosis and malignant transformation in HCV infected patients. The expression of miR-182 and miR-150 was evaluated using real-time quantitative PCR (qRT-PCR) in 120 subjects: 40 HCC patients, 40 hepatitis C patients (20 cirrhotic and 20 non-cirrhotic HCV genotype 4) and 40 healthy controls. In HCC, statistically significant decrease of miR-182 and miR-150 compared to non-cirrhotic HCV patients (p = 0.015, p = 0.006 respectively) and of miR-150 compared to controls (p = 0.039). In cirrhotic HCV patients, significant down regulation of miR-182 and miR-150 compared to non-cirrhotic HCV (p = 0.003, p = 0.024 respectively). On the other hand, significant upregulation of miR-182 was observed in non-cirrhotic HCV compared to controls (p = 0.036). Alpha-fetoprotein (AFP) showed sensitivity 15% for HCC diagnosis at the cut-off value of 400 ng/ml, while combining AFP with miR-182 and miR-150, resulted in improving sensitivity to (90%) and diagnostic accuracy to (80%). miR-182 and miR-150 can be used as non invasive biomarkers for HCC and combination of these miRNAs and AFP markedly improve the diagnosis of HCC. Both miR-182 and miR-150 can also be used as predictive markers for detection of cirrhosis progression in HCV infected patients.

摘要

在埃及,肝脏疾病的发病率极高,保持着全球丙型肝炎病毒 (HCV) 感染率最高的纪录,并呈肝细胞癌 (HCC) 发病率上升的趋势。现有的诊断方法在 HCC 的早期诊断中表现不佳。导致 HCV 发展的确切致病因素仍不清楚。microRNA 已被报道为癌症诊断和病毒-宿主相互作用的有前途的生物标志物。本研究旨在检测 miR-182 和 miR-150 作为 HCV 感染患者肝硬化和恶性转化发展的生物标志物的作用。使用实时定量 PCR (qRT-PCR) 评估 120 名受试者的 miR-182 和 miR-150 表达:40 名 HCC 患者、40 名丙型肝炎患者(20 名肝硬化和 20 名非肝硬化 HCV 基因型 4)和 40 名健康对照者。在 HCC 中,与非肝硬化 HCV 患者相比,miR-182 和 miR-150 的表达水平显著降低(p=0.015,p=0.006),与对照组相比,miR-150 的表达水平显著降低(p=0.039)。在肝硬化 HCV 患者中,与非肝硬化 HCV 患者相比,miR-182 和 miR-150 的表达水平显著下调(p=0.003,p=0.024)。另一方面,与对照组相比,非肝硬化 HCV 患者中 miR-182 的表达水平显著上调(p=0.036)。甲胎蛋白 (AFP) 在 AFP 截断值为 400ng/ml 时,对 HCC 诊断的敏感性为 15%,而将 AFP 与 miR-182 和 miR-150 联合使用可将敏感性提高至 90%,诊断准确性提高至 80%。miR-182 和 miR-150 可作为 HCC 的非侵入性生物标志物,联合使用这些 miRNA 和 AFP 可显著提高 HCC 的诊断。miR-182 和 miR-150 也可作为 HCV 感染患者检测肝硬化进展的预测标志物。

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