Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling
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DOI:
10.3892/ol.2012.810
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发表时间:
2012-10-01
期刊:
影响因子:
2.9
通讯作者:
Tanaka, Hiroshi
Tanaka, Hiroshi
中科院分区:
医学4区
文献类型:
--
作者:
Katayama, Yuki;Maeda, Moegi;Tanaka, Hiroshi

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肝细胞癌(Hepatocellular carcinoma,HCC)是最常见的肝脏恶性肿瘤之一。由于术后复发和肝内转移的发生率高,术后5年生存率低。为了研究HCC进展的分子机制,mRNA以及microRNA(miRNA)表达水平已经在各种研究中进行了分析。然而,以前的研究还没有使用肿瘤和周围非肿瘤组织以及正常肝脏样本全面比较具有各种临床特征的HCC患者中miRNA的表达。在这项研究中,我们分析了40例具有异质性发病机制的HCC患者的肿瘤和非肿瘤组织以及6例转移性肝癌患者的周围非肿瘤组织中miRNA的表达。为了鉴定每种疾病状态的特异性miRNAs,我们全面比较了各种组合中miRNAs的表达。结果表明,与B型肝炎患者相比,丙型肝炎病毒感染患者中许多已知的以及新的miRNAs的表达发生了改变。病毒,没有任何病毒感染。以下miRNA在肿瘤和非肿瘤组织中下调,因此可以作为慢性肝病的新生物标志物:miR-18 b *,miR-296- 5 p,miR-557,miR-581,miR-625*,miR-1228,miR-1249和miR-2116*。类似地,miR-129*、miR-146 b-3 p和miR-448是HCC生物标志物的新候选者,而与病毒感染无关。
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the liver. Since postoperative recurrence and intrahepatic metastases occur frequently, the postoperative 5-year survival rate is low. To investigate the molecular mechanisms of HCC progression, mRNA as well as microRNA (miRNA) expression levels have been profiled in various studies. However, no previous study has comprehensively compared the expression of miRNAs in HCC patients with various clinical features using the tumor and surrounding non-tumor tissues and normal liver samples. In this study, we profiled the expression of miRNAs in tumor and non-tumor tissues from 40 HCC patients with heterogeneous pathogenesis and 6 surrounding non-tumor tissues from patients with metastatic liver cancer. To identify miRNAs specific to each disease state, we comprehensively compared the expression of miRNAs in various combinations. The results indicate that the expression of many known as well as novel miRNAs was altered in patients with the hepatitis C virus infection compared with those with the hepatitis B. virus and without any virus infection. The following miRNAs were downregulated in the tumor and non-tumor tissues, and thus could serve as novel biomarkers for chronic liver diseases: miR-18b*, miR-296-5p, miR-557, miR-581, miR-625*, miR-1228, miR-1249 and miR-2116*. Similarly, miR-129*, miR-146b-3p and miR-448 are novel candidates for HCC biomarkers regardless of virus infection.