Complications of Cirrhosis in American Patients

描述(由申请人提供)： 肝细胞癌是美国发病率上升最快的一种肿瘤，预计这一趋势将在未来20年内持续下去。这是一种致命的肿瘤，只有大约10%的患者有资格接受治疗、干预、移植或手术切除)。肝癌的发病率和死亡率是一样的，因为目前诊断肝癌的工具：甲胎蛋白(AFP)和超声缺乏敏感性和特异性。因此，改进早期发现和识别最高风险人群的战略至关重要。这项建议的中心是验证新的血清标志物对早期肝细胞癌的诊断。将进行两项研究：病例对照研究和前瞻性队列研究。病例对照研究将纳入表现为肝细胞癌的患者作为病例，并纳入肝硬变队列研究中未发展为肝细胞癌的患者作为对照。根据UNOS TNM系统，早期肝细胞癌可分为I期和II期。初步研究表明，DES-γ-羧基凝血酶原(DCP)单独或与一种新的高尔基蛋白-73(GP73)联合应用对肝癌的诊断更为敏感和特异，但纳入的早期肝癌患者很少。在这项建议中，我将确定DCP、GP73和其他通过蛋白质组学鉴定的新的血清标志物，在早期肝癌的诊断中是否比AFP更敏感和特异。这项前瞻性队列研究将招募肝硬变和非肝癌患者，每6个月跟踪一次，最长达54个月，以确定DCP、GP73和其他血清标记物是否可以导致更早地诊断出肝癌。将获得人口统计学、病史、烟酒使用和实验室数据，以检查与肝细胞癌发展相关的危险因素。我的职业目标是成为一名独立成功的临床研究员，专注于肝细胞癌的早期发现。我认识到，为了实现我的目标，额外的教学培训以及在有经验的导师的指导下设计和进行临床研究的经验将是至关重要的。K23奖将提供对我的成功至关重要的保护时间。在资助期间，我将继续学习统计学和流行病学方面的其他课程。我将监督拟议研究的进行，并定期与我的导师和顾问会面。完成这项提议将使我能够实现我的职业目标，并为改善肝细胞癌患者的预后做出贡献。

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.