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: 7215129
• 负责人: ROBERT A FISHER
• 金额: $ 49.11万
• 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/7215129
• 关键词: Ablation; Biological Markers; 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; Genome; 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; Range; Recurrence; Risk; Role; Serum; Specimen; Subgroup; Survival Analysis; Time; Tissues; Transplant Recipients; Transplantation; Tumor stage; alpha-Fetoproteins; base; follow-up; liver biopsy; liver transplantation; outcome forecast; prevent; prospective; tumor progression

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感染导致肝硬化的患病率增加，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，以预防肝衰竭死亡。LT受到器官短缺的限制，高达30%的患者在等待供体时出现禁忌症。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。肝癌转移和复发的分子标志物可以为传统的临床和组织病理学提供更多的信息。功能.我们 将探讨一种假设，即建立一种基于分子的方法对诊断时的HCVHCC进行分类，将允许检测具有不同疾病的HCC患者的不同亚组，从而更准确地选择患者进行移植治疗。在本多中心前瞻性项目中，嵌套在A2 ALL NIH-NIDDK队列研究中，基因表达谱和全基因组洛分析将用于研究。我们建议：1-研究HCV-HCC启动（比较等待LT的有和没有HCC的HCV感染患者的基因表达谱和洛模式），并鉴定一组用于分类具有发展HCC潜力的高风险患者的重要基因; 2-分析疾病进展，建立用于区分具有发展HCC复发的最大风险的等待供体的HCV-HCC患者的分子指纹; 3-将研究目标2中建立的分子指纹，通过进行生存分析和比较按LDLT和死亡供体肝移植受体组分层的LT后HCC复发的风险来预测LT后结果的准确性。我们建议建立一种基于分子的方法，用于在诊断II时对HCV-HCC进行分类，允许检测具有不同疾病的HCC患者的不同亚组，从而更准确地选择患者进行移植治疗。