miRNA Biomarkers for Hepatocellular Carcinoma Associated with Viral Hepatitis

病毒性肝炎相关肝细胞癌的 miRNA 生物标志物

• 批准号: 8364566
• 负责人: THOMAS D. SCHMITTGEN
• 金额: $ 25.1万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364566
• 关键词: 3' Untranslated Regions; Accounting; Binding; Biological Assay; Biological Markers; Blinded; Blood; Blood Circulation; Body Fluids; Cancer Etiology; Cessation of life; Chronic Hepatitis B; Chronic Hepatitis C; Cirrhosis; Classification; Clinical Trials; Collection; Data; Development; Disease; Early Detection Research Network; Early Diagnosis; Evaluation; Goals; Grant; Hepatitis; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Incidence; Individual; Infection; Lead; Liquid substance; Liver; Malignant Neoplasms; Malignant neoplasm of liver; Messenger RNA; MicroRNAs; Monitor; Patient Monitoring; Patients; Pattern; Performance; Plasma; Population; Primary carcinoma of the liver cells; Proteins; Publishing; ROC Curve; Research; Resources; Risk Factors; Sampling; Sensitivity and Specificity; Serum; Solid Neoplasm; Specimen; Staging; Testing; Tissues; Training; Translations; Tumor Tissue; United States; Untranslated RNA; Validation; Viral; Viral hepatitis; Virus Diseases; alpha-Fetoproteins; cohort; data management; experience; prospective; validation studies

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.

描述（由申请人提供）：肝细胞癌（HCC）是全世界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类别之一，主要是因为丙型肝炎病毒 (HCV) 感染率不断上升。显然需要生物标志物来预测那些肝炎阳性个体在早期阶段发展为 HCC，而明确的治疗可能具有治愈性。循环 microRNA (miRNA) 作为癌症生物标志物具有巨大的潜力。目前还没有已发表的研究鉴定出感染 HCV 并发展为 HCC 的患者的血清或血浆 miRNA 特征。本研究旨在开发一种循环 miRNA 特征，用作 HCV 相关 HCC 的生物标志物。具体目标 1：目标 1 的目标是识别并验证 HCV 感染个体中 HCC 的 miRNA 特征。作为训练集，我们将分析来自 HCV 阳性个体的一组血浆样本中的 miRNA，其中一半是 HCC+（Mayo 队列）。然后，信息最丰富的 miRNA 将在一组测试血浆样本中得到验证。具体目标 2：目标 1 中鉴定的 miRNA 组将在第二组 100 个血清样本（EDRN 组）中进行验证。大约 60% 的 EDRN 参考集是 HCV 阳性。如果 miRNA 特征的表现等于或优于血清甲胎蛋白，我们将获得更大的 750 个血清样本的 EDRN 验证集。这项研究的成功完成将有助于在 HCC 发展之前对 HCV 感染个体的 miRNA 特征进行前瞻性收集和评估。 公众健康相关性：肝癌，其中 75% 以上是肝细胞癌 (HCC)，是美国增长最快的癌症死亡原因，并且已成为全球第三大最常见的癌症死亡原因。美国发病率增加的原因被认为主要是由于整个人口中丙型肝炎病毒（HCV）感染率的增加。目前缺乏有效、廉价的检测方法来监测 HCV+ 个体是否患有 HCC。生物标志物是监测这些患者的一种途径。最近作为生物标志物进行研究的分子之一是组织和体液（包括血液）中的 microRNA (miRNA)。这项研究将确定 HCV+ 个体发生 HCC 时血液中 miRNA 模式的变化，以便及早发现疾病并获得治愈性治疗。