Identification of microbial biomarkers for hepatocellular carcinoma in a multi-ethnic population of patients with nonalcoholic fatty liver disease

多种族非酒精性脂肪肝患者肝细胞癌微生物生物标志物的鉴定

• 批准号: 10305532
• 负责人: Shehnaz Khursheed Hussain
• 金额: $ 7.31万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10305532
• 关键词: Identification; microbial; biomarkers; hepatocellular; carcinoma

PROJECT SUMMARY/ABSTRACT Nonalcoholic fatty liver disease (NAFLD) related hepatocellular carcinoma (HCC) is a growing public health problem, and the burden is disproportionately carried by racial and ethnic minority populations. There is an urgent need to gain a better understanding of the underlying biological mechanisms responsible for why some people with NAFLD are more prone to developing HCC, and the causes for disparities in NAFLD related HCC. Experimental data show that the composition and products of the gut microbiome, many of which have established relationship with obesity and/or a high fat diet, are carcinogenic to the liver. Our preliminary data suggest that there are ethnic differences in microbial composition in a cirrhotic population at high risk for HCC, and that certain metabolites can differentiate cirrhotics with HCC from those without HCC. In the proposed case-control study, we will examine the contributions of race/ethnicity, fecal microbiome, fecal metabolome, and host factors (e.g. specific dietary factors and markers of body and liver fat composition) to NAFLD related HCC. Importantly, we have constructed a multi-disciplinary and collaborative research team with the required scientific expertise in microbiology, informatics, statistics, cancer epidemiology, and NAFLD biology; and the right clinical partnerships to succeed with the targeted patient recruitment required to address the specific aims. We will recruit 225 study participants with NAFLD and with HCC (N=75) and without HCC (N=150), over 1.25 months. Participants will be recruited from two neighboring clinical centers that care for a large proportion of Hispanics and African Americans in Los Angeles, two groups that are at the highest risk for HCC and stand to gain the most from the proposed research. Study participants will provide fecal, urine, and blood specimens; epidemiological data; clinical data; and nutritional data. Over the last 6 months of the project, we will perform laboratory testing and statistical modeling. We will use a combination of mixed effects logistic regression models, and integrative analytic approaches, to understand the contribution of our laboratory, epidemiological, and clinical data to NAFLD-HCC. The information gained from this study may open prospects for therapeutic interventions that could delay or avert HCC in these vulnerable at-risk populations.

项目总结/摘要 非酒精性脂肪性肝病（NAFLD）相关的肝细胞癌（HCC）是一个日益增长的公共卫生 这一问题，而且负担不成比例地由少数种族和族裔人口承担。有一个 迫切需要更好地了解导致一些人死亡的潜在生物学机制。 NAFLD患者更容易发生HCC，以及NAFLD相关HCC差异的原因。 实验数据表明，肠道微生物组的组成和产物，其中许多具有 与肥胖和/或高脂肪饮食的关系，对肝脏有致癌作用。我们的初步数据 提示在HCC高危人群中微生物组成存在种族差异， 并且某些代谢物可以区分患有HCC的患者和没有HCC的患者。拟议 病例对照研究中，我们将检查人种/种族，粪便微生物组，粪便代谢组， 和宿主因素（例如特定的饮食因素和身体和肝脏脂肪组成的标志物）与NAFLD相关 HCC。重要的是，我们已经建立了一个多学科和合作的研究团队， 微生物学、信息学、统计学、癌症流行病学和NAFLD生物学方面的科学专长; 正确的临床合作伙伴关系，以成功地进行针对性的患者招募， 目标。我们将招募225名患有NAFLD和HCC（N=75）以及没有HCC（N=150）的研究参与者，超过 1.25个月参与者将从两个相邻的临床中心招募，这些中心照顾大部分患者。 在洛杉矶的西班牙裔和非洲裔美国人中，这两个群体患HCC的风险最高， 从拟议的研究中获得最大收益。研究参与者将提供粪便、尿液和血液标本; 流行病学数据;临床数据;和营养数据。在项目的最后6个月，我们将执行 实验室测试和统计建模。我们将使用混合效应逻辑回归的组合 模型和综合分析方法，以了解我们的实验室，流行病学， 和NAFLD-HCC的临床数据。从这项研究中获得的信息可能会开辟治疗的前景。 在这些脆弱的高危人群中，可以延迟或避免HCC的干预措施。