Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K
Laboratory of Human Tumor Virus, Institute for Viral Research, Kyoto University, Kyoto, Japan.
Oncogene. 2006 Apr 20;25(17):2537-45. doi: 10.1038/sj.onc.1209283.
MicroRNAs (miRNAs) are a non-coding family of genes involved in post-transcriptional gene regulation. These transcripts are associated with cell proliferation, cell differentiation, cell death and carcinogenesis. We analysed the miRNA expression profiles in 25 pairs of hepatocellular carcinoma (HCC) and adjacent non-tumorous tissue (NT) and nine additional chronic hepatitis (CH) specimens using a human miRNA microarray. Targets and references samples were co-hybridized to a microarray containing whole human mature and precursor miRNA sequences. Whereas three miRNAs exhibited higher expression in the HCC samples than that in the NT samples, five miRNAs demonstrated lower expression in the HCC samples than in the NT samples (P<0.0001). Classification of samples as HCC or NT by using support vector machine algorithms based on these data provided an overall prediction accuracy of 97.8% (45/46). In addition, the expression levels of four miRNAs were inversely correlated with the degree of HCC differentiation (P<0.01). A comparison of CH and liver cirrhosis samples revealed significantly different pattern of miRNA expression (P<0.01). There were no differences, however, between hepatitis B-positive and hepatitis C-positive samples. This information may help clarify the molecular mechanisms involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.
微小RNA(miRNA)是一类参与转录后基因调控的非编码基因家族。这些转录本与细胞增殖、细胞分化、细胞死亡和致癌作用相关。我们使用人类miRNA微阵列分析了25对肝细胞癌(HCC)及相邻非肿瘤组织(NT)以及另外9份慢性肝炎(CH)标本中的miRNA表达谱。将靶标样本和对照样本共同与包含整个人类成熟和前体miRNA序列的微阵列进行杂交。结果显示,有3种miRNA在HCC样本中的表达高于NT样本,而有5种miRNA在HCC样本中的表达低于NT样本(P<0.0001)。基于这些数据,使用支持向量机算法将样本分类为HCC或NT,总体预测准确率为97.8%(45/46)。此外,4种miRNA的表达水平与HCC分化程度呈负相关(P<0.01)。CH样本和肝硬化样本的比较显示,miRNA表达模式存在显著差异(P<0.01)。然而,乙肝阳性样本和丙肝阳性样本之间没有差异。这些信息可能有助于阐明肝病进展所涉及的分子机制,有望作为HCC的诊断工具。