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，美国肝细胞癌 (HCC) 的发病率正在上升。手术切除（SR）和肝移植（LT）仍然是唯一可能治愈的治疗方法。由于美国 80% 的 HCC 患者患有肝硬化，因此最佳护理需要分析癌症分期以预测复发，并确定肝脏储备以预测 SR 与 LT 的适用性，以防止因肝衰竭而死亡。 LT 受到器官短缺的限制，高达 30% 的患者在等待捐赠者期间出现该手术的禁忌症。活体肝移植（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愈性治疗至关重要。 HCC 转移和复发的分子标志物可以为传统临床和组织病理学获得的信息提供额外的信息。特征。我们 将探索这样一种假设，即在诊断时建立基于分子的 HCVHCC 分类方法将允许检测具有不同预后的 HCC 患者的不同亚组，从而更准确地选择接受移植治疗的患者。在这个多中心前瞻性项目中，嵌套在 A2ALL NIH-NIDDK 队列研究中，基因表达谱和全基因组 LOH 分析将用于研究。我们建议： 1- 研究 HCV-HCC 起始（比较等待 LT 的 HCV 感染患者和未患 HCC 的基因表达谱和 LOH 模式），并确定一组重要基因，用于对可能发生 HCC 的高危患者进行分类; 2-分析疾病进展，建立分子指纹来区分等待 HCC 复发风险最大的捐赠者的 HCV-HCC 患者； 3-将研究目标 2 中建立的分子指纹，通过执行生存分析并比较按 LDLT 和已故供体肝移植受者组分层的 LT 后 HCC 复发风险，预测 LT 后结果的准确性。我们建议在诊断 II 时建立基于分子的 HCV-HCC 分类方法，可以检测具有不同预后的 HCC 患者的不同亚组，从而更准确地选择接受移植治疗的患者。