Project 3: Tumor-associated biomarkers for HIV-associated Diffuse Large B-cell Lymphoma in Malawi and South Africa

项目 3：马拉维和南非 HIV 相关弥漫性大 B 细胞淋巴瘤的肿瘤相关生物标志物

• 批准号: 10084559
• 负责人: Yuri Fedoriw
• 金额: $ 24.77万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-13 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10084559
• 关键词: AIDS-Related Lymphoma; Achievement; Africa South of the Sahara; Age; Aging; Appearance; Behavioral; Bioinformatics; Biological; Biological Factors; Biological Markers; Cancer Etiology; Caring; Cessation of life; Characteristics; Clinical; Clinical Research; Clinical Trials Design; Cohort Studies; Collaborations; Core Facility; Country; DNA Sequencing Facility; Data; Diagnosis; Environment; Epidemic; Expression Profiling; Future; Gene Expression; Genes; Genomics; Goals; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Histologic; Hospitals; Immune; Immune System Diseases; Immunocompetent; Immunogenomics; Immunologics; Incidence; Income; Individual; Inflammatory; Infrastructure; Kaposi Sarcoma; Lymphoma; Lymphomagenesis; Malawi; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Molecular; Molecular Analysis; Newly Diagnosed; Outcome; Patient-Focused Outcomes; Patients; Pattern; Population; Population Growth; Prognostic Marker; Prospective cohort; Regional Disease; Research; Resources; Risk Factors; Risk stratification; Site; South Africa; Speed; Tissue Sample; Translational Research; Tumor Biology; Universities; Vulnerable Populations; Work; advanced analytics; base; cancer risk; chemotherapy; clinical diagnostics; clinical remission; cohort; comparison group; differential expression; experience; improved; improved outcome; individualized medicine; innovation; insight; large cell Diffuse non-Hodgkin' s lymphoma; low income country; outcome forecast; prognostic; prospective; response; routine care; scale up; screening; sociodemographic factors; specific biomarkers; transcriptome; transcriptome sequencing; tumor; tumor microenvironment; tumor-immune system interactions; virology

ABSTRACT: PROJECT 3: Tumor-associated biomarkers for HIV-associated Diffuse Large B-cell Lymphoma in Malawi and South Africa Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to epidemic levels of HIV infection, population growth, and aging. Diffuse large B-cell lymphoma (DLBCL) is highly associated with HIV, the commonest lymphoma subtype among HIV-infected individuals, and the commonest cause of cancer death among people living with HIV in high-income countries (HIC). Despite histologically similar appearances, HIV- associated DLBCL differs biologically from DLBCL in immunocompetent populations and may also differ within HIV-infected populations depending on the HIV immunologic and virologic environment in which they occur. However, current diagnosis, risk stratification and therapy do not account for these differences which remain incompletely understood, and suitable patient cohorts to overcome these challenges have historically been lacking. Our long-term goal is to improve outcomes for HIV-associated DLBCL in SSA by applying promising regionally generated biomarkers, building on our previous immunophenotypic and molecular analyses of DLBCL from the region, to a prospective cohort of patients in Malawi and South Africa. The work will further characterize tumor microenvironmental factors that influence tumor biology across the spectrum of HIV- associated immune dysfunction. We hypothesize that prognostic biomarkers can be identified and implemented in SSA to better tailor treatment for this challenging and vulnerable population. Given the generalized HIV epidemic in the region, comparisons within specific tumor types based on HIV status are uniquely possible in this setting. Similar studies are challenging to conduct in the US, given relatively few HIV- positive cancers, and differences between the HIV-infected and general HIV-negative US population with respect to age, as well as behavioral and other cancer risk factors. These efforts will be enhanced by established collaborations with bioinformatics and sequencing core facilities, allowing the proposed research to yield insights which inform the care of HIV-associated DLBCL worldwide. The proposed work is necessary to understand the biological factors underlying lymphomagenesis and improve survival for HIV-associated DLBCL in high- and low-income countries.

摘要：项目3：与HIV相关的大型B细胞的肿瘤相关生物标志物 马拉维和南非的淋巴瘤 由于艾滋病毒感染的流行水平，撒哈拉以南非洲（SSA）的淋巴瘤发病率正在增加 人口增长和衰老。扩散的大B细胞淋巴瘤（DLBCL）与HIV高度相关， HIV感染的个体中最常见的淋巴瘤亚型，也是癌症死亡的最常见原因 在高收入国家（HIC）的艾滋病毒中的人们中。尽管组织学相似，但HIV- 在免疫能力人群中，相关的DLBCL与DLBCL在生物学上不同，并且在 艾滋病毒感染的人群取决于发生的HIV免疫和病毒学环境。 但是，当前的诊断，风险分层和治疗并不能解决这些差异 不完全理解，合适的患者队列克服这些挑战一直存在 缺乏。我们的长期目标是通过应用有希望的 以我们先前的免疫表型和分子分析为基础的区域生成的生物标志物 DLBCL从该地区到马拉维和南非的前瞻性患者队列。这项工作将进一步 表征肿瘤微环境因素，这些因素会影响HIV范围的肿瘤生物学 相关的免疫功能障碍。我们假设可以识别预后生物标志物，并且 在SSA中实施，以更好地针对这个具有挑战性和脆弱的人群量身定制治疗。鉴于 该地区普遍化的HIV流行，基于HIV状况的特定肿瘤类型的比较是 在这种情况下独特。鉴于相对较少的HIV- 阳性癌症以及HIV感染和一般HIV阴性的美国人群之间的差异 尊重年龄以及行为和其他癌症风险因素。这些努力将通过 与生物信息学和测序核心设施建立了合作，使拟议的研究能够 产生洞察力，这些见解为全球与HIV相关的DLBCL提供服务。拟议的工作是必要的 了解淋巴作用的生物因素并改善与HIV相关的DLBCL的生存率 在高收入和低收入国家。