The UCLA Center in Early Detection of Liver Cancer

项目摘要 肝癌是癌症死亡的第二大常见原因。虽然癌症死亡率一直在下降 总体而言，由于肥胖和酒精的发病率不断增加，肝癌死亡率一直在稳步上升。 虐待这种高死亡率主要是由于早期发现方面的挑战。该项目的目标是整合 肝细胞癌（HCC）早期检测的分子、影像学和临床信息。在 在上一个资助期，我们开发了一种高度敏感和具有成本效益的方法， 用于癌症检测的甲基化组，并已成功验证了试点HCC与肝硬化的技术 队列。我们还建立了多个临床队列来研究HCC检测，包括前瞻性研究。 肝硬化或HBV患者的纵向HCC筛查队列。血液样本的可用性，成像 这些队列中患者的扫描和全面的临床信息为我们提供了独特的机会 在下一个资助期内，发展一套综合癌症检测方法。加州大学洛杉矶分校的中心包括一个 临床和转化研究人员的多学科团队，我们在下一次资助中有以下重点 阶段：（1）继续扩大多个临床队列，以促进肝癌的早期发现。这些 群组将为拟议的研究和其他联合体范围的项目提供宝贵的资源。（二） 持续的实验和计算开发，以完善用于早期癌症的cfDNA甲基化组测定 侦测在实验上，我们将解决基于cfDNA的早期癌症检测的关键挑战，即， 有限的cfDNA输入，并且在计算上，除了DNA甲基化之外，我们还将从 分析数据以增强癌症检测。(3)我们将整合表观基因组学、影像学和临床信息 成为检测HCC的补充方法。我们将建立病因特异性模型，用于多- 模态数据，以最大限度地提高性能。(4)我们将为联合会的合作活动作出贡献。我们有 积极参与联盟内外的合作。我们是一个活跃的 我们将与其他中心合作， 多组学和多模态标记物，以开发血液样本和成像数据的诊断潜力。

Project Summary Liver cancer is the second most frequent cause of cancer deaths. While cancer mortality has been declining overall, liver cancer mortality has been rising steadily due to the increasing incidence of obesity and alcohol abuse. This high mortality is mainly due to challenges in early detection. The goal of this project is to integrate molecular, imaging, and clinical information for the early detection of Hepatocellular Carcinoma (HCC). In the previous grant period, we developed a highly sensitive and cost-effective method of using cell-free DNA methylome for cancer detection, and have successfully validated the technology on a pilot HCC versus cirrhosis cohort. We have also established multiple clinical cohorts to study HCC detection, including a prospective longitudinal HCC screening cohort of patients with cirrhosis or HBV. The availability of blood samples, imaging scans, and comprehensive clinical information of patients in those cohorts provide us with unique opportunities to develop an integrated cancer detection method in the next funding period. The UCLA center includes a multidisciplinary team of clinical and translational researchers, and we have the following foci in the next funding period: (1) Continued expansion of multiple clinical cohorts to facilitate early detection of liver cancer. These cohorts shall provide an invaluable resource for the proposed research and other consortium-wide projects. (2) Continued experimental and computational development to refine the cfDNA methylome assay for early cancer detection. Experimentally, we will address a key challenge in cfDNA-based early cancer detection, namely, the limited cfDNA input, and computationally we will extract additional features, in addition to DNA methylation, from the assay data to enhance cancer detection. (3) We will integrate epigenomic, imaging, and clinical information into a complementary approach for the detection of HCC. We will build etiology-specific models for the multi- modality data to maximize performance. (4) We will contribute to collaborative consortium activities. We have been enthusiastically participating in collaborations within and beyond the consortium. We are an active enrollment site for the consortium-wide clinical cohorts, and we will collaborate with other centers to develop multi-omics and multi-modality markers to exploit the diagnostic potential of blood samples and imaging data.