Identification of microRNAs specifically expressed in hepatitis C virus-associated hepatocellular carcinoma.

Identification of microRNAs specifically expressed in hepatitis C virus-associated hepatocellular carcinoma.
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DOI:
10.1002/ijc.28075
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发表时间:
2013-08-15
影响因子:
6.4
通讯作者:
Farci, Patrizia
Farci, Patrizia
中科院分区:
医学1区
文献类型:
--
作者:
Diaz, Giacomo;Melis, Marta;Tice, Ashley;Kleiner, David E.;Mishra, Lopa;Zamboni, Fausto;Farci, Patrizia

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尽管有几项研究调查了 miRNA 与肝细胞癌 (HCC) 的关联,但迄今为止发表的数据并不一致。造成这些差异的原因可能是大多数研究使用 HCC 病灶周围的非肿瘤组织作为对照,而 HCC 病灶几乎总是受到肝硬化或慢性肝炎以及其他病理状况(如乙型肝炎病毒 (HBV) 或丙型肝炎病毒 (HCV) 感染)的影响。此外,无论病毒病因如何,HCC 通常都作为一个组进行分析。在本研究中,我们通过将肿瘤组织与广泛的肝脏标本进行比较,研究了 HCV 相关 HCC 中差异表达的 miRNA,这些标本包括从肝脏捐献者和接受血管瘤肝切除术的患者获得的健康肝脏,以及各种急慢性肝病的组织,包括与 HCC 无关的 HCV 相关肝硬化、与 HCC 相关的 HCV 相关肝硬化。 HCC 和 HBV 相关的急性肝衰竭 (ALF)。我们的研究检查了微阵列平台上可用的整套 2,226 个人类 miRNA,包括 1,121 个 pre miRNA 和 1,105 个成熟 miRNA。应用严格的统计方法将错误发现的风险降低到 1% 以下。我们的数据鉴定了 18 个仅在 HCV 相关 HCC 中表达的 miRNA,其特点是相对于所有其他肝脏疾病和健康状况具有高特异性和选择性,并连接到以 p53、磷酸酶和张力蛋白同源物 (PTEN) 和全反式视黄酸信号传导为中心的调控网络。
Although several studies have investigated the association of miRNAs with hepatocellular carcinoma (HCC), the data published so far are not concordant. A reason for these discrepancies may be the fact that most studies used as a control the non-tumorous tissue surrounding the HCC lesion, which is almost invariably affected by cirrhosis or chronic hepatitis, as well as other pathological conditions such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Moreover, HCC is often analyzed as a single group regardless of the different viral etiologies. In this study, we investigated miRNAs differentially expressed in HCV-related HCC by comparing the tumorous tissues to a wide range of liver specimens, including healthy livers obtained from liver donors and patients who underwent liver resection for angioma, in addition to tissues from various acute and chronic liver diseases, including HCV-related cirrhosis not associated with HCC, HCV-related cirrhosis associated with HCC, and HBV-associated acute liver failure (ALF). Our study examined the whole set of 2,226 human miRNAs, including 1,121 pre miRNAs and 1,105 mature miRNAs, available in a microarray platform.Stringent statistical methods were applied to reduce the risk of false discoveries to less than 1%. Our data identified 18 miRNAs exclusively expressed in HCV-associated HCC, characterized by high specificity and selectivity versus all other liver diseases and healthy conditions, and connected into a regulatory network pivoting on p53, phosphatase and tensin homolog (PTEN), and all-trans retinoic acid signaling.
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