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首页> 外文期刊>International Journal of Cancer =: Journal International du Cancer >Hepatic miR-126 is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma
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Hepatic miR-126 is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma

机译:肝miR-126是用于检测乙型肝炎病毒感染肝细胞癌的潜在血浆生物标志物

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Controversies about the origin of circulating miRNAs have encouraged us to identify organ specific circulating miRNAs as disease biomarkers. To identify liver-specific miRNAs for hepatocellular carcinoma (HCC), global expression profiling of miRNAs in liver tissue of HBV-HCC and HBV-control with no or mild fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Among ten highly altered miRNAs, six miRNAs were successfully validated in tissues, whereas only two miRNAs, miR-126 and miR-142-3p showed increased expression in plasma of HBV-HCC compared to HBV-non-HCC patients. Subsequently, ROC curve analysis revealed that neither miR-126 nor miR-142-3p performed better than AFP in discriminating HCC from non-HCC while combination of each with AFP showed significantly higher efficiency rather than AFP alone (AUC: 0.922, 0.908 vs. 0.88; sensitivity: 0.84, 0.86 vs. 0.82 and specificity: 0.92, 0.94 vs. 0.86 respectively). Interestingly, triple combination of markers (miR-126 +/- miR-142-3p +/- AFP) showed no additive effect on efficiency (AUC: 0.925) over the dual combination. Again, the expression of only miR-126 was noticed significantly higher in HBV-HCC patients with low-AFP [< 250 ng/ml] compared to either non-HCC or liver cirrhosis (AUC: 0.77, 0.64, respectively). Furthermore, no alteration in expression of mir-126 in HCV-HCC or non-viral-HCC revealed that miR-126 + AFP might be specific to HBV-HCC. To understand the physiological role of these two miRNAs in hepato-carcinogenesis, target genes related to cancer pathways (APAF1, APC2, CDKN2A, IRS1, CRKL, LIFR, EGR2) were verified. Thus, combination of circulating miR-126 +/- AFP is a promising noninvasive diagnostic biomarker for HBV-HCC and may be useful in the management of HCC patients.
机译:关于循环miRNA的起源的争议鼓励我们识别器官特异性循环miRNA作为疾病生物标志物。为了鉴定肝细胞癌(HCC)的肝细胞特异性miRNA,评估HBV-HCC和NO或轻度纤维化的HBV-HCC和HBV对照中的MIRNA的全局表达分析。在HCC中鉴定了共40种差异表达的miRNA。在十个高度改变的miRNA中,在组织中成功验证了六种miRNA,而仅与HBV-非HCC患者相比,只有两个miRNA,miR-126和miR-142-3p显示出HBV-HCC血浆的表达增加。随后,ROC曲线分析显示,MIR-126和MIR-142-3P既比AFP在鉴别非HCC鉴别HCC时表现优于AFP,同时每种AFP的组合显示出明显更高的效率而不是单独的AFP(AUC:0.922,0.908。 0.88;灵敏度:0.84,0.86 vs.0.82和特异性:0.92,0.94与0.86分别)。有趣的是,标记的三倍组合(miR-126 +/- miR-142-3p +/- afp)显示了对双组合的效率(AUC:0.925)的添加剂效果。同样,与非HCC或肝硬化(AUC:0.77,0.64分别)相比,仅注意到患有低AFP [250 ng / mL]的HBV-HCC患者的MIR-126的表达明显高。此外,HCV-HCC或非病毒-HCC中MIR-126的表达没有改变,显示MIR-126 + AFP可能是HBV-HCC的特异性。为了了解这两种MiRNA在肝癌中的生理作用,验证了与癌症途径(APAF1,APC2,CDKN2A,IRS1,CRK1,LEVR,EGR2)相关的靶基因。因此,循环miR-​​126 +/- AFP的组合是HBV-HCC的有望的非侵入性诊断生物标志物,可用于HCC患者的管理。

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