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: 7589742
• 负责人: ROBERT A FISHER
• 金额: $ 47.23万
• 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/7589742
• 关键词: Ablation; Caring; Cessation of life; Characteristics; Cirrhosis; Classification; Clinical; Cohort Studies; Detection; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease Progression; Excision; Gene Expression; Gene Expression Profiling; Genes; Genetic Markers; HCV Cirrhosis; Hepatic; Hepatitis C; Hepatitis C virus; Incidence; Liver; Liver Failure; Living Donors; Malignant Neoplasms; Methods; Molecular; Molecular Profiling; Neoplasm Metastasis; Operative Surgical Procedures; Organ; Outcome; Outcome Measure; Patient Selection; Patients; Pattern; Prevalence; Primary carcinoma of the liver cells; Procedures; RNA; Radiology Specialty; Recurrence; Risk; Role; Serum; Specimen; Subgroup; Survival Analysis; Time; Tissues; Transplant Recipients; Transplantation; Tumor stage; alpha-Fetoproteins; base; follow-up; genome-wide; high risk; liver biopsy; liver transplantation; molecular marker; outcome forecast; prevent; prospective; tumor progression

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 HCV- HCC 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 multi- enter 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 j'ngerprint 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 .iver 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.

在美国，由于患病率的增加，肝细胞癌（HCC）的发病率正在上升 丙型肝炎病毒感染导致的肝硬化手术切除（SR）和肝移植（LT）仍然是唯一的 潜在的治愈性治疗。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，测定肝脏储备以预测适用性 预防肝衰竭死亡。LT受到器官短缺的限制，高达30%的 病人在等待捐献者时出现手术禁忌症。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是 这对提供潜在的治愈性治疗至关重要。肝癌转移和复发的分子标志物 可以提供额外的信息，从传统的临床和组织病理学。功能.我们 将探讨建立一种基于分子的HCV分类方法的假设， 诊断时的HCC将允许检测具有不同病变的HCC患者的不同亚组， 允许在选择患者进行移植治疗时更精确。在这个多- 进入前瞻性项目，嵌套在A2 ALL NIH-NIDDK队列研究中，基因表达谱和 全基因组洛缺失分析将用于研究。我们提出：1-研究HCV-HCC的启动 （比较HCV感染伴和不伴HCC患者的基因表达谱和洛模式 等待LT），并确定一组重要的基因，用于分类高风险患者， 发展HCC; 2-分析疾病进展，建立分子指纹以区分 等待供体的HCV-HCC患者发生HCC复发的风险最大; 3-分子水平 将研究目标2中建立的j 'ngerprint通过执行以下操作预测LT后结局的准确性： 生存分析和比较按LDLT和死亡供体分层的LT后HCC复发风险 .艾弗移植受体群体。 我们建议建立一种基于分子水平的HCV-HCC诊断分型方法 II允许检测具有不同预后的HCC患者的不同亚组，从而允许更大的 选择移植治疗患者的准确性。