Genes Related to HCC Progression in LD and DD Transplant

LD 和 DD 移植中与 HCC 进展相关的基因

• 批准号: 7092812
• 负责人: ROBERT A FISHER
• 金额: $ 56.76万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7092812
• 关键词: clinical research; disease /disorder classification; disease /disorder proneness /risk; gene expression profiling; genetic markers; hepatitis C virus; hepatocellular carcinoma; human subject; liver cirrhosis; liver transplantation; loss of heterozygosity; method development; neoplasm /cancer genetics; neoplasm /cancer relapse /recurrence; neoplastic growth; patient oriented research; prognosis; single nucleotide polymorphism; tissue donors

DESCRIPTION (provided by applicant): The incidence of hepatocellular carcinoma (HCC) is rising in the USA because of the increased prevalence of cirrhosis from HCV infection. Surgical resection (SR) and liver transplantation (LT) still represent the only potentially curative treatments. Since 80% of HCC patients in the USA have cirrhosis, optimum care requires the analysis of cancer stage to predict recurrence, and the determination of liver reserve to predict suitability of SR vs. LT to prevent death from liver failure. LT is limited by the shortage of organs, with up to 30% of patients developing contraindications to the procedure while waiting for a donor. Living Donor Liver Transplant (LDLT) is one way to shorten the waiting time. Accurate tumor staging in patients with HCC is critical to provide a potentially curative treatment. Molecular markers for HCC metastasis and recurrence could provide additional information to that gained from traditional clinical and histopathological. features. We will explore the hypothesis that establishment of a molecular-based method for the classification of HCVHCC at diagnosis will permit the detection of distinct subgroups of HCC patients with different prognoses,- allowing greater accuracy in the selection of patients for treatment cure with transplantation. In this multicenter prospective project, nested within the A2ALL NIH-NIDDK Cohort Study, gene expression profiling and genome-wide LOH analysis will be used for the studies. We propose: 1- To study HCV-HCC initiation (comparing gene expression profiles and LOH patterns in HCV infected patients with and without HCC awaiting LT) and to identify a set of significant genes for classifying high-risk patients with a potential for developing HCC; 2-To analyze disease progression, establishing a molecular fingerprint for distinguishing HCV-HCC patients awaiting a donor with the greatest risk for developing HCC recurrence; 3-The molecular fingerprint established in aim 2 will be studied for it's accuracy to predict outcomes post-LT by performing survival analysis and comparing the risk of post-LT HCC recurrence stratified by LDLT and Deceased Donor Liver Transplant recipient groups. We propose that establishment of a molecular-based method for the classification of HCV-HCC at diagnosis II permit the detection of distinct subgroups of HCC patients with different prognoses, allowing greater accuracy in selection of patients for treatment cure with transplantation.

描述（由申请人提供）：由于HCV感染引起的肝硬化患病率增加，肝细胞癌（HCC）的发生率正在上升。手术切除（SR）和肝移植（LT）仍然代表唯一的潜在治疗方法。由于80％的HCC患者患有肝硬化，因此最佳护理需要对癌症阶段进行分析以预测复发，并确定肝脏储备以预测SR与LT的适用性，以防止肝脏衰竭死亡。 LT受到器官短缺的限制，在等待捐赠者时，多达30％的患者为该手术开发了禁忌症。活着的供体肝移植（LDLT）是缩短等待时间的一种方法。 HCC患者的准确肿瘤分期对于提供潜在的治疗治疗至关重要。 HCC转移和复发的分子标记物可以为从传统的临床和组织病理学中获得的其他信息提供其他信息。特征。我们 将探讨以下假设：建立一种基于分子的方法来诊断HCVHCC的分类方法将允许检测不同预后的HCC患者的不同亚组，这可以在选择治疗治疗的患者中的精确度。在嵌套在A2ALL NIH-NIDDK队列研究中的这个多中心前瞻性项目中，基因表达分析和全基因组LOH分析将用于研究。我们提出：1-研究HCV-HCC的启动（比较有或没有HCC的HCV感染患者的基因表达谱和LOH模式），并确定一组重要基因，用于对具有开发HCC潜力的高危患者进行分类； 2分析疾病进展，建立一个分子指纹，用于区分HCV-HCC患者，等待具有最大风险发展HCC复发风险的供体的患者； 3-将研究在AIM 2中建立的分子指纹，以通过进行生存分析并比较LDLT和已故供体肝移植受体分层的LT HCC复发的风险来预测LT的准确性。我们建议建立一种基于分子的方法来诊断时HCV-HCC分类II允许检测不同预后不同的HCC患者的不同亚组，从而使选择患者的治疗治疗方法更准确。