Complications of Cirrhosis in American Patients

美国患者肝硬化的并发症

• 批准号: 6858708
• 负责人: JORGE A MARRERO
• 金额: $ 13.23万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858708
• 关键词: alcoholism /alcohol abuse; alpha fetoprotein; biomarker; blood tests; cancer risk; case history; clinical research; diagnosis design /evaluation; disease /disorder etiology; early diagnosis; glycoproteins; hepatocellular carcinoma; human population study; human subject; liver cirrhosis; longitudinal human study; obesity; patient oriented research; postdoctoral investigator; proteomics; prothrombin; questionnaires; serology /serodiagnosis; tobacco abuse

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is a tumor with the most rapid increase in incidence in the United States and this trend is expected to continue over the next 2 decades. It is a deadly tumor with only about 10% patients eligible for curative intervention transplantation or surgical resection). The incidence and death rates of HCC are equal because current tools for the diagnosis of HCC: alpha-fetoprotein (AFP) and ultrasound lack sensitivity and specificity. Therefore, strategies to improve the early detection and to identify those at the highest risk are of paramount importance. This proposal is centered on the validation of novel serum markers for the diagnosis of early HCC. Two studies will be conducted: a case-control study and a prospective cohort study. The case-control study will enroll patients presenting with HCC as cases and patients in the cirrhosis cohort study, who have not developed HCC as controls. Early HCC includes stage I and II HCC according to UNOS TNM system. Preliminary studies showed that des-gamma carboxyprothrombin (DCP), alone or in combination with a novel Golgi Protein-73 (GP73) are more sensitive and specific in the diagnosis of HCC but very few patients with early HCC were included. In this proposal, I will determine if DCP, GP73, and other novel serum markers identified through proteomics, alone or in combination will be more sensitive and specific than AFP in the diagnosis of early HCC. The prospective cohort study will enroll patients with cirrhosis and no HCC followed every 6 months for up to 54 months to determine if DCP, GP73 and other serum markers can lead to the diagnosis of HCC earlier. Demographics, medical history, tobacco and alcohol use, and laboratory data will be obtained to examine risk factors associated with HCC development. My career goal is to be an independently successful clinical investigator focused on early detection of HCC. I recognize that to achieve my goal, additional didactic training and experience in design and conduct of clinical studies under the guidance of accomplished mentors will be crucial. The K23 award will provide the protected time that is critical to my success. During the funding period, I will pursue additional courses in statistics and epidemiology. I will supervise the conduct of the proposed research and meet with my mentors and advisors regularly. Completing this proposal will allow me to achieve my career goal and to contribute to an improve outcome of patients with HCC.

描述（由申请人提供）： 肝细胞癌（HCC）是一种肿瘤，在美国发病率最快，预计该趋势将在未来20年中持续下去。它是一种致命的肿瘤，仅有约10％的患者有资格进行治疗干预移植或手术切除）。 HCC的发病率和死亡率是相等的，因为当前诊断HCC的工具：α-抗蛋白蛋白（AFP）和超声缺乏敏感性和特异性。因此，改善早期检测并确定处于最高风险的策略至关重要。该建议集中在验证新型血清标志物以诊断早期HCC的验证。将进行两项研究：一项病例对照研究和一项前瞻性队列研究。病例对照研究将招募患有HCC为病例的患者，并参与cirhosis队列研究的患者，他们尚未开发HCC作为对照。根据UNOS TNM系统，早期HCC包括I期和II期HCC。初步研究表明，单独或与新型高尔基蛋白73（GP73）单独或与新型HCC诊断更敏感和特异性的Des-Gamma羧基凝血酶（DCP）（DCP），但包括很少有早期HCC的患者。在此提案中，我将确定DCP，GP73和其他通过蛋白质组学鉴定的新型血清标记是否在诊断早期HCC的诊断中比AFP更敏感和特异性。这项前瞻性队列研究将招募肝硬化患者，每6个月内每6个月内无HCC，最多54个月，以确定DCP，GP73和其他血清标记是否可以较早地诊断出HCC。人口统计学，病史，烟草和酒精使用以及将获得实验室数据，以检查与HCC开发相关的危险因素。我的职业目标是成为一名专注于早期发现HCC的独立成功的临床研究者。我认识到，要实现我的目标，在成熟导师的指导下设计和进行临床研究的额外教学培训和经验至关重要。 K23奖将为我的成功至关重要的受保护时间。在资助期间，我将探讨统计和流行病学的其他课程。我将监督拟议的研究的行为，并定期与导师和顾问会面。完成这项建议将使我能够实现自己的职业目标，并为HCC患者的结果改善做出贡献。