微小RNA-150在肝细胞癌中的表达及其临床意义

Expression and clinical significance of mi R-150 in hepatocellular carcinoma

目的探讨微小RNA(mi R)-150在肝细胞癌中的表达及其临床意义。方法实时荧光定量聚合酶链反应(q RT-PCR)检测肝癌及配对癌旁组织中mi R-150表达。原位杂交技术(ISH)进一步验证肝癌和配对癌旁组织mi R-150表达差异。将肝癌组织中mi R-150表达与临床病理特征进行关联分析。Kaplan-Meier法检测mi R-150阴性组和阳性组生存曲线。Cox单因素回归模型分析mi R-150表达与患者术后总生存的相关性。结果 q RT-PCR结果显示:与癌旁组织相比,12例中有8例肝癌组织低表达mi R-150,肝癌组织中mi R-150表达明显降低(P=0.034)。ISH结果与q RT-PCR结果相一致,即肝癌组织大部分为阴性或弱阳性表达,62%癌旁组织ISH染色强度高于配对的肝癌组织(P<0.001)。关联分析提示mi R-150表达与AFP、肿瘤大小、TNM分期、组织学分级、脉管癌栓存在明显负相关(P<0.05)。mi R-150阳性组患者术后总生存明显高于mi R-150阴性组(P=0.004,Kaplan-Meier法)。Cox单因素回归分析提示肝癌组织低表达mi R-150是患者不良预后指标(P=0.005)。结论肝癌组织低表达mi R-150与肿瘤侵袭表型相关,提示不良预后。

Objectives To investigate the expression and clinical significance of mi R-150 in hepatocellular carcinoma（HCC）. Methods mi R-150 expression in liver cancer and paired normal tumor-adjacent tissues was determined by quantitative Real-time PCR（q RT-PCR）. The expression difference between HCC and tumor-adjacent tissues was further verified using in situ hybrization（ISH）technique. Association of mi R-150 expression in HCC tissues with clinicopathological status was examined by correlation analysis. Prognostic significance of mi R-150 expression in HCC samples was detected with Kaplan-Meier method and Cox regression analysis. Results q RT-PCR assay showed 8 /12 HCC cases had lower mi R-150 expression compared with tumor-adjacent tissues and mi R-150 expression level in HCC tissues markedly decreased（P =0.034）. Similar to q RT-PCR results, ISH technique demonstrated most HCC specimens had negative or weak staining of mi R-150, and staining intensity in 62% tumor-adjacent tissues was much higher than that in paired HCC tissues（P〈0.001）.Correlation analysis suggested mi R-150 expression was significantly negatively correlated with AFP level, tumor size, TNM stage, histological grade and intravascular thrombus（P 0.05）. Postoperative overall survival（OS） of mi R-150 positive group was much longer that of mi R-150 negative group（P =0.004, Kaplan-Meier method）. Cox univariate regression analysis implicated low mi R-150 level in HCC samples was an unfavorable prognostic indicator（P=0.005）. Conclusion Low expression of mi R-150 in HCC specimens is related with a more aggressive tumor phenotype and indicates poor prognosis for HCC patients.