肝细胞癌
小RNA
乙型肝炎病毒
塔克曼
肝硬化
生物标志物
医学
实时聚合酶链反应
乙型肝炎
病毒
免疫学
病毒学
内科学
生物
基因
生物化学
作者
Limin Liu,Zhibin Hu,Zhenxian Zhou,Xi Chen,Fen-Yong Liu,Junfeng Zhang,Hongbing Shen,Chenyu Zhang,Ke Zen
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2010-12-01
卷期号:70 (23): 9798-9807
被引量:417
标识
DOI:10.1158/0008-5472.can-10-1001
摘要
Abstract Diagnosis of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), particularly HCC independent of cirrhosis etiology, presents a great challenge because of a lack of biomarkers. Here we test the hypothesis that expression profiles of microRNAs (miRNAs) in serum can serve as biomarkers for diagnosis of HBV infection and HBV-positive HCC. We recruited 513 subjects (210 controls and 135 HBV-, 48 hepatitis C virus (HCV)-, and 120 HCC-affected individuals) and employed a strategy of initial screening by Solexa sequencing followed by validation with TaqMan probe-based quantitative reverse transcription-PCR assay. First, because of a close link between chronic hepatitis B and HCC, we compared miRNA expression profiles in HBV serum with that in control serum and successfully obtained 13 miRNAs that were differentially expressed in HBV serum. This 13-miRNA–based biomarker accurately discriminated not only HBV cases from controls and HCV cases, but also HBV-positive HCC cases from control and HBV cases. Second, we directly compared miRNA expressions in HCC serum with those in controls and identified 6 miRNAs that were significantly upregulated in HCC samples. Interestingly, 2 of these miRNAs, miR-375 and miR-92a, were also identified by our first approach as HBV specific. When we employed 3 of these miRNAs (miR-25, miR-375, and let-7f) as biomarkers, we could clearly separate HCC cases from controls, and miR-375 alone had an ROC of 0.96 (specificity: 96%; sensitivity: 100%) in HCC prediction. In conclusion, our study demonstrates for the first time that serum miRNA profiles can serve as novel and noninvasive biomarkers for HBV infection and HBV-positive HCC diagnosis. Cancer Res; 70(23); 9798–807. ©2010 AACR.
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