Use of Peripheral Blood Mononuclear Cells Mitochondrial DNA Content to Detect Hepatocellular Carcinoma in Hepatitis B Virus Infected Nigerians.

项目总结 这项为期五年的职业发展申请的研究将调查诊断的准确性 微创外周血单个核细胞线粒体DNA含量的研究 检测乙肝病毒-肝细胞癌的诊断试验。申请人--拉赫马特·阿德图图·阿迪萨 尼日利亚-2019年和2020年是Fogarty研究员，目前是NIH/FIC(D43TW010934)的实习生。 她提交这份K43的总体目标是成为一名独立的基础翻译科学家，拥有独特的 有兴趣询问线粒体的机械目的和作为治疗的目标，以减轻 肝癌在非洲的祸害。为了实现她设定的目标，她将获得新的能力来加强 她目前在1)临床和翻译研究方法；2)分子生物学和基因组学方面的能力 线粒体研究技术；3)数据管理和统计分析；4)科学写作 和仁慈精神。在拟议的研究中，她将招募慢性乙肝(CHB)和肝癌患者在两个月内 在尼日利亚拉各斯的胃肠病诊所，并根据AIM 1确定PBMC mtDNA含量是否可以 用更好的方法成功区分活动性乙肝病毒+/肝细胞癌+与慢性乙肝感染患者和未感染对照 诊断性能与当前方法的比较。在目标2下，她将确定PBMC mtDNA 在乙肝相关的肝细胞癌和慢性乙肝感染的患者中，含量可以预测肝细胞癌的严重程度。她还会 调查任何相关的危险因素，包括年龄、性别、饮酒、吸烟等可能预测或 影响严重程度。在AIM 3中，她将识别和评估mtDNA 4977碱基对(BP)缺失的频率 在与乙肝病毒相关的肝细胞癌、乙肝病毒感染者和健康参与者的PBMC中，并提供确证片段 通过序列分析的证据。这项研究将是尼日利亚和撒哈拉以南地区的第一项研究 这项研究结果的总体公共卫生意义是需要小的组织样本来 分析，易于获取外周血进行采样，以及预期的便利性和安全性 作为筛查工具的PBMC mtDNA可以为政策转变提供动力，倡导及早 用线粒体DNA含量筛查肝细胞癌候选人将利用资源、研究和 能力建设培训将通过此应用程序受益，75%的受保护时间支持由HER提供 她在美国、印度和印度的导师团队提供的导师支持、经验和专业知识 尼日利亚将获得新的职业发展技能，以成功过渡到独立的基础 翻译研究人员，这是本应用程序的首要目标。

Project summary The research in this five-year career development application will investigate the diagnostic accuracy of mitochondrial DNA content of peripheral blood mononuclear cells (MtDNA-PBMCs) as a minimally invasive diagnostic test for detecting HBV-hepatocellular carcinoma (HCC). The applicant - Rahmat Adetutu Adisa from Nigeria - was a Fogarty Fellow in 2019 and 2020 and is currently a trainee on an NIH/FIC (D43TW010934). Her overall goal for this K43 submission is to become an independent basic translational scientist with a unique interest in interrogating the mitochondria for mechanistic purposes and as therapeutic targets for alleviating the scourge of liver cancer in Africa. To achieve her set goals, she will acquire new competencies to strengthen her current capabilities in 1) Clinical and translational research methods; 2) Molecular biology and genomics techniques in mitochondrial research; 3) Data management and statistical analyses; and 4) Scientific writing and grantsmanship. In the proposed study, she will enroll chronic hepatitis B (CHB) and HCC patients at two gastroenterology clinics in Lagos, Nigeria, and determine under AIM 1 whether PBMC mtDNA content can successfully differentiate active HBV+/HCC+ from CHB-infected patients and uninfected controls with a better diagnostic performance compared to current methods. Under Aim 2, she will determine whether PBMC mtDNA content can predict the severity of HCC in HBV-associated HCC and in CHB-infected patients. She will also investigate any associated risk factors including age, gender, alcohol intake, smoking that may predict or impact severity. In AIM 3 she will identify and evaluate the frequencies of mtDNA 4977 base pair (bp) deletions in the PBMC of HBV-associated HCC, CHB-infected, and healthy participants and provide confirmatory pieces of evidence through sequence analysis. This study AIM would be the first in Nigeria and sub-Saharan Africa.The overall public health significance of findings from this study is the small tissue samples required for analysis, the easy accessibility of peripheral blood for sampling, and the anticipated convenience and safety of PBMC mtDNA as a screening tool which can provide the impetus for policy shift to advocate for early screening of HCC using the mtDNA content. The candidate will leverage on the resources, research and capacity building trainings to be availed through this application, 75% protected time support provided by her institution, the mentorship support, experience and expertise of her team of mentors in the US, India, and Nigeria to acquire new career development skills for a successful transition to an independent basic translational researcher which is the overarching goal of this application.