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

利用外周血单核细胞线粒体 DNA 含量检测乙型肝炎病毒感染的尼日利亚人的肝细胞癌。

• 批准号: 10734089
• 负责人: RAHMAT ADETUTU ADISA
• 金额: $ 11.7万
• 依托单位: COLLEGE OF MEDICINE, UNIVERSITY OF LAGOS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-27 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734089
• 关键词: Ablation; Accreditation; Advocate; Africa; Africa South of the Sahara; Age; Alcohol consumption; Award; Base Pairing; Biological Markers; Biopsy; Blood Vessels; Blood specimen; Chronic Hepatitis B; Clinic; Clinical Research; Cohort Studies; Competence; Contracts; Data; Detection; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Early Diagnosis; Early identification; Enrollment; Frequencies; Gastroenterology; Gender; Genetic; Genomics; Goals; Health Policy; Health care facility; Healthcare Systems; Hepatitis B Infection; Hepatitis B Virus; Hepatology; Histologic; India; Institution; Invaded; Investigation; Ionizing radiation; K-Series Research Career Programs; Lesion; MRI Scans; Malignant Neoplasms; Malignant neoplasm of liver; Mentors; Mentorship; Methods; Mitochondria; Mitochondrial DNA; Modality; Molecular; Molecular Biology; Neoplasm Metastasis; Nigeria; Nigerian; Nodule; Normal Range; Outcomes Research; Oxidative Stress; Participant; Patient Care; Patients; Performance; Peripheral Blood Mononuclear Cell; Persons; Ploidies; Policies; Population; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Public Health; Radiation exposure; Research; Research Activity; Research Methodology; Research Personnel; Research Project Summaries; Resource-limited setting; Resources; Risk; Risk Factors; Safety; Scanning; Scourge; Screening procedure; Sensitivity and Specificity; Sequence Analysis; Serum; Severities; Smoking; Specificity; Statistical Data Interpretation; Techniques; Testing; Time; Tissue Sample; Tissues; Training; Training Activity; Translating; Translational Research; Tumor Markers; United States National Institutes of Health; Vaccination; Work; Writing; X-Ray Computed Tomography; aged; alpha-Fetoproteins; arm; bench to bedside; career development; comparative; cost; data management; detection method; diagnostic accuracy; diagnostic biomarker; early detection biomarkers; early screening; effectiveness evaluation; experience; hazard; health practice; improved; interest; low and middle-income countries; minimally invasive; novel; participant enrollment; peripheral blood; programs; screening; sex; skill acquisition; skills; therapeutic target; translational scientist; treatment center; ultrasound

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.

项目摘要 这项为期五年的职业发展应用研究将调查以下诊断的准确性： 外周血单个核细胞（MtDNA-PBMCs）的线粒体DNA含量作为微创 用于检测HBV-肝细胞癌（HCC）的诊断测试。申请人- Rahmat Adetutu Adisa，来自 尼日利亚-在2019年和2020年是福格蒂研究员，目前是NIH/FIC（D43 TW 010934）的实习生。 她提交K43的总体目标是成为一名独立的基础翻译科学家， 感兴趣的询问线粒体的机械目的，并作为治疗目标，以减轻 肝癌在非洲肆虐。为了实现她设定的目标，她将获得新的能力，以加强 她目前在1）临床和转化研究方法; 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 还有格兰比亚在这项拟议的研究中，她将在两个月后招募慢性B型肝炎（CH B）和肝癌患者。 在尼日利亚的拉各斯的胃肠病学诊所，并根据AIM 1确定PBMC mtDNA含量是否可以 成功区分活动性HBV+/HCC+与CHB感染患者和未感染对照， 与现有方法相比，诊断性能。根据目标2，她将确定PBMC mtDNA是否 含量可以预测HBV相关HCC和CHB感染患者中HCC的严重程度。她还将 调查任何相关的风险因素，包括年龄，性别，饮酒，吸烟， 影响严重性。在AIM 3中，她将识别和评估线粒体DNA 4977个碱基对（bp）缺失的频率 在HBV相关HCC、CHB感染者和健康受试者的PBMC中， 通过序列分析找到证据这项研究AIM将是第一个在尼日利亚和撒哈拉以南地区 这项研究结果的总体公共卫生意义在于， 分析，外周血采样的容易获得性，以及预期的便利性和安全性， PBMC mtDNA作为一种筛查工具，可以为政策转变提供动力，以倡导早期 用mtDNA含量筛查HCC。候选人将利用资源，研究和 通过此应用程序提供的能力建设培训，由她提供75%的保护时间支持 她的导师团队在美国、印度和 尼日利亚获得新的职业发展技能，成功过渡到独立的基本 翻译研究员，这是本申请的首要目标。