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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

基本信息

批准号：
8520269
负责人：
THOMAS D. SCHMITTGEN
金额：
$ 16.77万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8520269
关键词：
3&apos 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

项目摘要

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.

描述（由申请人提供）：肝细胞癌（HCC）是全球第三大常见癌症死亡原因。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。存在一个明显的需要，生物标志物，可以预测那些肝炎阳性的个人发展肝癌在早期阶段时，明确的治疗是潜在的治愈。循环microRNA（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已经在HCV感染的患者中鉴定出血清或血浆miRNA特征，这些患者继续发展为HCC。这项研究旨在开发一种循环miRNA签名，用作HCV相关HCC的生物标志物。具体目标1：目标1的目标是鉴定和验证HCV感染个体中HCC的miRNA特征。作为训练集，我们将分析来自HCV阳性个体的血浆样品队列中的miRNA，其中一半是HCC+（马约队列）。然后将在血浆样品的测试组中验证信息量最大的miRNA。具体目标2：目标1中鉴定的一组miRNA将在第二组100份血清样品（EDRN组）中进行验证。大约60%的EDRN参考集为HCV阳性。如果miRNA签名的表现等于或优于血清甲胎蛋白，我们将被授权访问一个更大的EDRN验证集的750个血清样本。这项研究的成功完成将导致在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。