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.

项目概要 这项为期五年的职业发展应用研究将调查诊断的准确性 外周血单个核细胞 (MtDNA-PBMC) 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 - 曾于 2019 年和 2020 年成为 Fogarty 研究员，目前是 NIH/FIC (D43TW010934) 的实习生。 她这次提交 K43 的总体目标是成为一名独立的基础转化科学家，具有独特的能力 有兴趣出于机械目的询问线粒体并将其作为缓解症状的治疗靶点 非洲肝癌的祸害。为了实现她的既定目标，她将获得新的能力来加强 她目前在 1) 临床和转化研究方法方面的能力； 2) 分子生物学和基因组学 线粒体研究技术； 3）数据管理和统计分析； 4）科学写作 和赠款。在拟议的研究中，她将在两点招募慢性乙型肝炎 (CHB) 和 HCC 患者。 尼日利亚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，并具有更好的 与现有方法相比的诊断性能。在目标 2 下，她将确定 PBMC mtDNA 是否 内容可以预测 HBV 相关 HCC 和 CHB 感染患者的 HCC 严重程度。她也会 调查任何相关的风险因素，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，她将识别并评估 mtDNA 4977 碱基对 (bp) 缺失的频率 在 HBV 相关 HCC、CHB 感染者和健康参与者的 PBMC 中进行检测，并提供证实性片段 通过序列分析获得证据。这项 AIM 研究将是尼日利亚和撒哈拉以南地区的首项研究 非洲。这项研究结果的总体公共卫生意义在于，需要小组织样本 分析、外周血取样的方便性以及预期的便利性和安全性 PBMC mtDNA作为筛查工具，可以为政策转变提供动力，倡导早期治疗 使用 mtDNA 含量筛查 HCC。候选人将利用资源、研究和 通过此应用程序可获得能力建设培训，她提供 75% 的受保护时间支持 她在美国、印度和印度的导师团队提供的指导支持、经验和专业知识 尼日利亚将获得新的职业发展技能，以成功过渡到独立基础 转化研究员是此应用程序的总体目标。