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

项目摘要/摘要 非酒精性脂肪性肝病(NAFLD)相关性肝细胞癌(HCC)是一个日益严重的公共卫生问题 这是一个严重的问题，而且这一负担不成比例地由种族和少数民族人口承担。有一个 迫切需要更好地了解导致某些疾病的潜在生物学机制 非酒精性脂肪肝患者更容易发生肝细胞癌，这也是非酒精性脂肪肝相关肝细胞癌差异的原因。 实验数据显示，肠道微生物群的组成和产物，其中许多都有 与肥胖和/或高脂肪饮食的既定关系，对肝脏具有致癌作用。我们的初步数据 提示在肝癌高危人群中，肝硬变人群的微生物组成存在种族差异， 某些代谢产物可以区分有肝细胞癌的肝硬变患者和无肝细胞癌的肝硬变患者。在建议的 病例对照研究，我们将检查种族/民族，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记物)与NAFLD相关 肝细胞癌。重要的是，我们已经建立了一支多学科的协作研究团队，拥有所需的 在微生物学、信息学、统计学、癌症流行病学和NAFLD生物学方面的科学专长；以及 正确的临床合作伙伴关系，以成功地招募目标患者，以解决特定的 目标。我们将招募225名患有NAFLD和肝细胞癌(N=75)和非肝细胞癌(N=150)的研究参与者， 1.25个月。参与者将从两个相邻的临床中心招募，这两个中心的服务比例很大 在洛杉矶的西班牙裔和非裔美国人中，有两个群体患肝癌的风险最高 以便从拟议的研究中获得最大收益。研究参与者将提供粪便、尿液和血液样本； 流行病学数据、临床数据和营养数据。在项目的最后6个月里，我们将执行 实验室测试和统计建模。我们将使用混合效应Logistic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、 和临床资料对非酒精性脂肪肝-肝癌。从这项研究中获得的信息可能会打开治疗的前景 可以延迟或避免这些脆弱的高危人群中的肝细胞癌的干预措施。

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.