The interplay of social and molecular determinants in lung cancer disparity

肺癌差异中社会和分子决定因素的相互作用

• 批准号: 10364112
• 负责人: Brian M. Rivers
• 金额: $ 58.93万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364112
• 关键词: Address; Affect; African American population; American; Apoptosis; Aspirate substance; Behavioral Sciences; Bioinformatics; Biologic Characteristic; Biological; Biological Factors; Biological Markers; Biometry; Biopsy; Blood; Bronchoscopy; CCL20 gene; Cancer Biology; Cancer Patient; Cancer cell line; Caring; Cell Line; Cell Proliferation; Cells; Censuses; Characteristics; Chronic stress; Cigarette; Classification; Clinical Trials; Code; Computer software; Consent; Consumption; Data; Data Analyses; Diagnosis; Disease; Disease Outcome; Enrollment; Enzyme-Linked Immunosorbent Assay; Ethnic group; European; Evidence based intervention; Gender; Gene Expression Profiling; Goals; Hospitals; Hydrocortisone; Immune; Immune system; Immunity; Immunologics; Immunophenotyping; Immunotherapy; Incidence; Individual; Interdisciplinary Study; Investigational Drugs; Knowledge; Ligands; Link; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Metabolic; Metabolism; Methods; Molecular; National Institute on Minority Health and Health Disparities; Neighborhoods; Nodal; Non-Small-Cell Lung Carcinoma; Oncology; Outcome; Pathology; Pathway interactions; Patients; Phenotype; Physiology; Prognosis; Prognostic Marker; Proteins; Public Health; Race; Research; Risk; Risk Factors; Role; Saliva; Sampling; Serum; Shapes; Smoking; Social Characteristics; Socioeconomic Status; Stress; Supporting Cell; The Cancer Genome Atlas; Tissues; Tumor Immunity; Tumor Tissue; Tumor stage; Tumor-infiltrating immune cells; Visit; Work; base; beta-Chemokines; cancer health disparity; cancer immunobiology; cancer therapy; chemokine; chemokine receptor; cohort; design; detection method; disparity reduction; effective therapy; ethnic disparity; evidence base; improved; lung cancer cell; mortality; multidisciplinary; patient stratification; patient subsets; peripheral blood; racial difference; racial disparity; recruit; social; social factors; social interventions; social stress; stemness; success; targeted treatment; therapeutic biomarker; therapeutic target; therapy outcome; trait; transcriptome; treatment response; tumor

Abstract African Americans (AAs) are disproportionally affected by lung cancer, compared with all other racial and ethnic groups in terms of incidence and survival. Disproportionate diagnosis of aggressive disease and poor survival among AAs highlights the critical need for further studies that characterize racial differences in lung cancer. Our goal is to address this vital knowledge gap by identifying molecular, biological, and social characteristics (neighborhood-level factors) underlying the disease’s aggressiveness, thereby reducing the disparity between African Americans (AAs) and European Americans (EAs). Our central hypothesis is that CC chemokine receptor-6 (CCR6) and its only natural ligand CCL20 add to the racial difference in molecular footprint and immune landscape, impacting racial disparity in lung cancer aggressiveness and prognosis. In addition to these biological factors, social factors associated with chronic stress, which elevated cortisol, shape the immunological landscape differently in AAs, contributing to racial differences in aggressiveness and prognosis. There is a unique possibility that CCR6/CCL20 and social characteristics contribute to the disparity in lung cancer among AAs, which has never been explored. Hence the proposed work will enhance understanding of cell biological traits of aggressive lung cancers, particularly non-small cell lung cancer (NSCLC), which accounts for ~85% of the lung cancers that underlie ethnic disparities in disease outcomes and mechanisms by which cells acquire aggressive phenotypes. To accomplish these goals, we have assembled a multidisciplinary research team with complementary expertise in cancer immuno-biology, oncology, pulmonary care, pathology, public health/behavioral science, bioinformatics, and biostatistics to investigate the following aims: A1. Establish the association of CCR6-CCL20 axis in NSCLC aggressiveness and therapeutic response among AAs and EAs; A2. Ascertain the race-specific differences in the immunological landscape contributing to the NSCLC disparity and A 3. Determine the impact of social stress on the immune signature among AA and EA NSCLC patients. Completion of these aims will i) inform a rapid, non-invasive chemokine based detection methods which will allow classifying potentially fatal lung cancers, ii) a method for early patient stratification so that risk-adapted chemokine-based therapies can be designed to match patient subgroups with distinct CCR6 profiles, iii) to offer more effective treatment approach, iv) a framework for improving the success rate of clinical trials involving investigational drugs by establishing new criteria for patient classification, Immune-based strategies to reduce disparity and, v) identify geospatial neighborhood characteristics impacting the immune system and outcome in lung cancer aggressiveness and therapeutic outcome on which evidence-based intervention can be developed to address the disparity in lung cancer.

摘要与所有其他种族相比，非裔美国人(AA)受到肺癌的影响不成比例。 和种族群体在发病率和存活率方面的差异。对侵袭性疾病的不成比例的诊断 AAS的存活率凸显了进一步研究肺部种族差异的迫切需要 癌症。我们的目标是通过确定分子、生物学和社会性来解决这一重要的知识鸿沟 疾病侵袭性的潜在特征(邻里因素)，从而减少了 非洲裔美国人(AA)和欧洲裔美国人(EA)之间的差距。我们的中心假设是CC 趋化因子受体-6(CCR6)及其唯一天然配体CCL20增加了分子足迹的种族差异 和免疫格局，影响肺癌侵袭性和预后的种族差异。除了……之外 这些生物因素，与慢性压力相关的社会因素，提高了皮质醇，塑造了 AAS的免疫状况不同，导致种族在侵袭性和预后上的差异。 有一种独特的可能性是CCR6/CCL20和社会特征导致了肺癌的差异 在AAA中，这是从未被探索过的。因此，拟议的工作将加强对CELL的了解 侵袭性肺癌的生物学特征，特别是非小细胞肺癌(NSCLC)，这是 约85%的肺癌是疾病结局和细胞机制存在种族差异的基础 获得攻击性表型。为了实现这些目标，我们集合了一个多学科的研究 在癌症免疫生物学、肿瘤学、肺部护理、病理学、公共卫生等领域拥有互补专业知识的团队 健康/行为科学、生物信息学和生物统计学，以调查以下目标：建立 CCR6-CCL20轴与非小细胞肺癌侵袭性和疗效的关系； A2.确定导致非小细胞肺癌差异的免疫环境中特定种族的差异 A3.确定社会压力对AA和EA非小细胞肺癌患者免疫信号的影响。 这些目标的完成将提供一种快速、非侵入性的基于趋化因子的检测方法，它将 允许对可能致命的肺癌进行分类，ii)一种早期患者分层的方法，以便适应风险 基于趋化因子的疗法可以设计成匹配具有不同CCR6特征的患者亚组，III)提供 更有效的治疗方法，四)提高临床试验成功率的框架，包括 研究药物通过建立新的患者分类标准，减少基于免疫的策略 差异和，v)确定影响免疫系统和结果的地理空间邻里特征 可开展循证干预的肺癌侵袭性和治疗结果 以解决肺癌之间的差异。