miRNA Biomarkers for Hepatocellular Carcinoma Associated with Viral Hepatitis

描述（由申请人提供）：肝细胞癌（HCC）是全球第三大最常见的癌症死亡原因。HCC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（HCV）感染率的增加。显然需要生物标志物来预测肝炎阳性的早期HCC患者，当最终治疗有可能治愈时。循环microRNAs （miRNAs）作为癌症生物标志物具有巨大的潜力。目前还没有发表的研究发现HCV感染患者发展为HCC的血清或血浆miRNA特征。本研究旨在开发一种循环miRNA标记，作为hcv相关HCC的生物标志物。特异性目的1：目的1是鉴定和验证hcv感染个体中HCC的miRNA特征。作为训练集，我们将分析HCV阳性个体血浆样本队列中的mirna，其中一半为HCC+ （Mayo队列）。最具信息量的mirna将在一组血浆样本中进行验证。特异性目标2：在目标1中鉴定的mirna将在第二组100个血清样本（EDRN队列）中进行验证。大约60%的EDRN参考组是HCV阳性。如果miRNA特征表现等于或优于血清α胎蛋白，我们将获得750个血清样本的更大的EDRN验证集。这项研究的成功完成将导致在HCC发展之前对hcv感染者的miRNA特征进行前瞻性收集和评估。

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. PUBLIC HEALTH RELEVANCE: Liver cancers, of which over 75% is hepatocellular carcinoma (HCC), are the fastest growing cause of cancer death in the United States and are already the third most common cause of cancer death worldwide. The cause for the increased incidence in the United States is thought to be largely from the increased Hepatitis-C virus (HCV) infection rate throughout the population. There is a lack of an efficent, inexpensive test to monitor HCV+ individuals for the development of HCC. Biomarkers are one avenue to monitor these patients. One of the most recent molecules to be studied as biomarkers are microRNA (miRNA) in the tissues and body fluids including the blood. This study will see to indentify how the miRNA pattern changes in the blood of HCV+ individuals when they develop HCC so that the disease may be found early and they can see curative treatment.