Racial Disparity of microRNA in Hepatitis C Virus Mediated Hepatocellularcarcinoma

丙型肝炎病毒介导的肝细胞癌中 microRNA 的种族差异

• 批准号: 8872288
• 负责人: Ratna B. Ray
• 金额: $ 21.25万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8872288
• 关键词: Address; African American; Area; Biological Markers; Biopsy Specimen; Caucasians; Chronic Hepatitis C; Data; Death Rate; Development; Disease Progression; Ethnic group; Genetic; Goals; Growth; Hepatitis C; Hepatitis C Incidence; Hepatitis C virus; Hepatocyte; Human; Laboratory Finding; Liver diseases; Malignant neoplasm of liver; Mediating; Medical; MicroRNAs; Modality; Molecular; Patients; Play; Primary carcinoma of the liver cells; Process; Race; Regulation; Research; Research Proposals; Risk Factors; Role; Serum; Staging; Therapeutic; Up-Regulation; Virus; caucasian American; cell growth; circulating microRNA; cohort; innovation; interest; liver biopsy; loss of function; public health relevance; racial disparity

 DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) mediated end stage liver disease, including hepatocellular carcinoma (HCC), is a growing problem among African Americans (AAs). The central goal of this project is to investigate the racial disparity of HCV mediated liver cancer. HCV infection mediated death rate among AA patients is about 2- fold higher than CA. Very little information is available about the underlying mechanisms of liver disease progression among chronically HCV infected ethnic groups. Our research proposal will examine this previously unexplored area of HCV mediated end stage liver disease among AA. microRNAs (miRNAs) play critical roles in multi-step cell growth regulatory processes, and the relationship between chronic HCV infection and miRNA expression is of considerable interest in understanding virus mediated disease progression. Our preliminary data indicated a group of microRNAs modulated in chronically HCV infected AA sera as compared to that of CA. We hypothesize that these circulatory miRNAs can be potential predictive biomarker towards HCC development in HCV infected AA patients, and are involved deregulating hepatocyte growth. Thus, identification of predictive biomarkers for HCC and the underlying molecular mechanisms for race disparity will have a great translational benefit. Our long term objectives are to translae these findings from the laboratory to the bedside identifying predictive biomarker, and developing therapeutic modalities for HCV mediated liver disease progression. Impact: The results from this R21 exploratory proposal will have a high impact by investigating the role of miRNAs as genetic factors for understating racial disparity. Our research will explain why African Americans have higher incidence of HCV mediated liver cancer as compared to Caucasians.

 描述(申请人提供)：丙型肝炎病毒(丙型肝炎病毒)介导的终末期肝病，包括肝细胞癌(肝细胞癌)，是一个日益严重的问题在非裔美国人(AA)。这个项目的中心目标是调查丙型肝炎病毒介导的肝癌的种族差异。再生障碍性贫血患者的丙型肝炎病毒感染介导性死亡率约为CA患者的2倍。关于慢性丙型肝炎病毒感染族群中肝病进展的潜在机制的信息很少。我们的研究计划将在再生障碍性贫血患者中检测这一先前未被发现的丙型肝炎介导的终末期肝病。MicroRNAs(MiRNAs)在细胞生长的多步调控过程中起着关键作用，而慢性丙型肝炎病毒感染与miRNA表达之间的关系对于了解病毒介导的疾病进展具有重要意义。我们的初步数据表明，与CA相比，在慢性丙型肝炎感染的AA血清中有一组microRNAs被调节。我们推测，这些循环中的miRNAs可能是预测丙型肝炎病毒感染的AA患者发生肝癌的潜在生物标志物，并参与解除对肝细胞生长的调节。因此，识别肝癌的预测生物标记物和种族差异的潜在分子机制将有很大的翻译好处。我们的长期目标是将这些发现从实验室转移到床边，识别预测性生物标记物，并开发丙型肝炎病毒介导的肝病进展的治疗方式。影响：这项R21探索性提案的结果将产生很高的影响，调查miRNAs作为低估种族差异的遗传因素的作用。我们的研究将解释为什么与高加索人相比，非裔美国人有更高的丙型肝炎病毒介导的肝癌发病率。