miRNA Biomarkers for Hepatocellular Carcinoma Associated with Viral Hepatitis

描述(申请人提供)：肝细胞癌是全球癌症死亡的第三大常见原因。肝癌是美国增长最快的癌症死亡群体之一，主要是因为丙型肝炎病毒(丙型肝炎病毒)感染率的增加。显然，需要生物标记物来预测那些肝炎阳性患者在最终治疗潜在治愈的早期阶段发展为肝细胞癌。循环中的microRNAs(MiRNAs)具有作为癌症生物标志物的巨大潜力。目前还没有发表的研究表明，在继续发展为肝细胞癌的丙型肝炎病毒感染患者中，存在血清或血浆miRNA特征。这项研究的目的是开发一种循环中的miRNA签名，作为丙型肝炎病毒相关肝癌的生物标志物。具体目标1：目标1的目标是识别和验证丙型肝炎病毒感染者肝细胞癌的miRNA签名。作为训练集，我们将分析来自丙型肝炎病毒阳性个体的一组血浆样本中的miRNAs，其中一半是肝细胞癌阳性(Mayo队列)。然后，将在一组血浆样本中验证最具信息量的miRNAs。具体目标2：目标1中确定的miRNAs小组将在第二个100个血清样本队列(EDRN队列)中进行验证。EDRN参考集合中约60%为丙型肝炎病毒阳性。如果miRNA签名的性能与血清甲胎蛋白相同或更好，我们将获得750个血清样本的更大EDRN验证集。这项研究的成功完成将导致在发生肝细胞癌之前对丙型肝炎病毒感染者的miRNA签名进行前瞻性的收集和评估。

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. HCC is among the fastest growing group of cancer deaths in the U.S mainly because of the increasing rate of hepatitis C viral (HCV)- infections. There exists an obvious need for biomarkers that could predict those hepatitis positive individuals who develop HCC at early stages when definitive therapy is potentially curative. Circulating microRNAs (miRNAs) hold great potential as cancer biomarkers. There are no published studies that have identified a serum or plasma miRNA signature in HCV infected patients that go on to develop HCC. This research aims to develop a circulating miRNA signature to be used as biomarkers for HCV-associated HCC. Specific Aim 1: The goal of Aim 1 is to identify and validate a miRNA signature for HCC in HCV-infected individuals. As the training set, we will profile miRNAs in a cohort of plasma samples from HCV positive individuals, half of which are HCC+ (Mayo cohort). The most informative miRNAs will then be validated in a testing set of plasma samples. Specific Aim 2: The panel of miRNAs identified in Aim 1 will be validated in a second cohort of 100 serum samples (EDRN cohort). Approximately 60% of the EDRN reference set is HCV positive. Should the miRNA signature perform equal to or better than that of serum alpha fetoprotein, we will be granted access to a larger EDRN validation set of 750 serum samples. Successful completion of this research will lead to prospective collection and evaluation of the miRNA signature in HCV-infected individuals prior to the development of HCC.