The UCLA Center in Early Detection of Liver Cancer

项目摘要/摘要 肝细胞癌是导致肝硬变患者死亡的主要原因。这种肿瘤与 肝硬变占90%以上的病例。一种在肝癌早期阶段准确检测的方法将极大地 提高对疾病的管理和治疗能力。加州大学洛杉矶分校的中心旨在开发一种有效和 负担得起的以血液为基础的肝癌早期检测方法。我们的团队由翻译和 在早期发现、生物标志物、癌症等领域拥有多学科专业知识的临床研究人员 监视、成像和生物库。我们将重点关注血液中循环的肿瘤DNA(CtDNA)。CtDNA 携带癌症特有的遗传和表观遗传学异常，这使得癌症的非侵入性“液体活组织检查”成为可能 诊断。我们的诊断测试是基于cfDNA的DNA甲基化模式。我们的集成计算 实验技术可以显著提高诊断能力，同时大幅降低成本。 我们有以下目标：(1)我们将建立一个肝硬变患者的纵向队列。肝硬变患者 将接受每6个月一次的超声成像筛查和血样采集。加州大学洛杉矶分校的肝脏 诊所每年接待约1200名肝硬变患者。(2)我们将建立一个最先进的生物质谱库 包括队列中个体的血浆、切除后的肝肿瘤组织和术后的肝硬变病变。 肝脏移植。(3)我们将进行第二阶段临床检测验证和第三阶段早期检测验证 用于诊断测试。(4)我们将为跨网络协作活动做出贡献。

PROJECT SUMMARY / ABSTRACT Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis in more than 90% of cases. A method of detecting HCC accurately in its early stages would greatly improve our ability to manage and treat the disease. The UCLA Center aims to develop an effective and affordable blood-based method for the early detection of liver cancer. Our team consists of translational and clinical researchers with multi-disciplinary expertise in the areas of early detection, biomarkers, cancer surveillance, imaging, and biorepositories. We will focus on circulating tumor DNA (ctDNA) in the blood. ctDNA carryies cancer-specific genetic and epigenetic aberrations, which enable a noninvasive `liquid biopsy' for cancer diagnosis. Our diagnostic test is based on the DNA methylation patterns of cfDNA. Our integrated computational and experimental technologies can significantly boost the diagnostic power while dramatically reducing the cost. We have the following aims: (1) We will establish a longitudinal cohort of cirrhotic patients. The cirrhotic patients will be subject to ultrasound imaging screening and blood sample collection every 6 months. The UCLA liver clinic sees ~1200 cirrhotic patients per year. (2) We will establish a state-of-the-art biospecimen repository that includes plasma from individuals in the cohort, tissue from liver tumors after resection, and cirrhotic lesions after liver transplantation. (3) We will perform Phase 2 clinical assay validation and Phase 3 early detection validation for the diagnostic test. (4) We will contribute to the collaborative trans-network activities.