Novel modalities for prostate cancer screening: mast cells as predictors of disease, disease aggressiveness and marks of disease disparity

前列腺癌筛查的新方法：肥大细胞作为疾病、疾病侵袭性和疾病差异标志的预测因子

• 批准号: 10650620
• 负责人: CAROLE A OSKERITZIAN
• 金额: $ 20.9万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650620
• 关键词: Address; Affect; African American; Age; Aging; Area; Benign; Biological; Biological Markers; Biopsy; Biopsy Specimen; Cancer Patient; Caregivers; Cell Aggregation; Cell Count; Cells; Clinic; Collection; Complex; Core Biopsy; Data; Data Analyses; Development; Diagnosis; Diagnostic; Disease; Disparity; Doctor of Medicine; Early Diagnosis; Endowment; Ethnic Population; Evaluation; Faculty; Feasibility Studies; Future; Gene Expression Profiling; Genes; Goals; Grant; Health; Human; Hypersensitivity; Image; Image Analysis; Incidence; Laboratories; Lesion; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical; Methods; Modality; Molecular; Molecular Profiling; Morbidity - disease rate; Mus; Nature; Normal tissue morphology; Oncogenic; Oncologist; Patients; Phenotype; Physicians; Pilot Projects; Population; Positioning Attribute; Predictive Value; Predisposition; Prevention; Property; Prostate; Prostatic; Prostatic Tissue; Race; Research; Risk; Sampling; Screening for Prostate Cancer; Site; Solid Neoplasm; Source; Sphingolipids; Survey Methodology; Testing; Tissues; United States; Urology; Variant; baby boomer; cancer diagnosis; cancer health disparity; caucasian American; clinically relevant; clinically significant; computerized; cost effective; disease disparity; first responder; functional status; high risk; human tissue; imaging modality; improved; innovation; insight; interest; mast cell; member; men; mortality; novel; overexpression; prisma; prostate biopsy; prostate cancer risk; quantitative imaging; racial disparity; racial population; screening; sphingosine 1-phosphate; success; tumor; urologic; validation studies

SUMMARY Prostate cancer (PCa) is the second most common cancer in men in the United States. The absolute number of men with PCa is projected to increase as a result of the ageing baby boomer population. However, the lack of reliable biomarkers for PCa screening has led to decreased early detection, particularly for African American (AA) men who have the highest PCa morbidity, metastatic risk and mortality rates than any other racial or ethnic group in the US. When cancer is suspected, patients must undergo multiple needle core biopsies because of the multifocal nature of PCa. Nonetheless, up to 34% of biopsied men are told they are cancer-free when they are not, because the biopsies missed the cancer foci. Hence, it is critical to better define the cellular and molecular features indicative of PCa development and risk for aggressive disease in benign biopsies of PCa patients to improve diagnosis and screening. In this grant, we are proposing to explore a variation on the concept of field effect in PCa, postulating that histopathologically benign looking prostate core biopsies may in fact feature alterations indicative of PCa and of PCa aggressiveness present in the same patient at another prostatic site, using age- and race-matched (AA and Caucasian Americans (CA)) sets of samples (benign and cancer-bearing biopsies for each patient). Prostate-resident mast cells (MC) aggregate in stromal, peritumoral and/or intratumoral areas but their clinical relevance remains controversial. Our preliminary data suggests the usefulness of establishing MC profiles in benign prostatic tissues of PCa patients. The objectives of this application are: to investigate MC functional profiles in benign human prostate tissues as predictors of PCa aggressiveness and candidate functional biomarkers of PCa race disparity; to define and validate a molecular signature indicative of PCa and PCa aggressiveness present in benign human prostate biopsies and test its predictive value for PCa disparity and association to MC; and apply our new screening modalities in clinics, contingent upon successful validation studies. We anticipate that our approach may improve diagnosis and screening for high-risk PCa and position MC as potential drivers of PCa disparity.

概括 前列腺癌 (PCa) 是美国男性中第二常见的癌症。绝对数量 由于婴儿潮一代人口老龄化，患有 PCA 的男性预计将会增加。然而，缺乏 用于 PCa 筛查的可靠生物标志物的使用导致早期检测率下降，特别是对于非裔美国人 (AA) 男性的 PCa 发病率、转移风险和死亡率高于任何其他种族或群体 美国的族裔群体。当怀疑患有癌症时，患者必须进行多次针芯活检 由于 PCa 的多灶性。尽管如此，高达 34% 的活检男性被告知他们没有癌症 但实际上并非如此，因为活组织检查错过了癌症病灶。因此，更好地定义 细胞和分子特征表明良性前列腺癌的发展和侵袭性疾病的风险 对 PCa 患者进行活检以改善诊断和筛查。在这笔赠款中，我们建议探索一个 PCa 场效应概念的变化，假设组织病理学上看起来良性的前列腺核心 事实上，活检可能具有表明 PCa 和 PCa 侵袭性存在于同一组织中的改变。 患者在另一个前列腺部位，使用年龄和种族匹配（AA 和高加索裔美国人 (CA)）组 样本（每位患者的良性和携带癌症的活组织检查）。前列腺肥大细胞 (MC) 聚集在 间质、瘤周和/或瘤内区域，但其临床相关性仍存在争议。我们的初步 数据表明在 PCa 患者的良性前列腺组织中建立 MC 谱是有用的。这 本申请的目的是：研究良性人类前列腺组织中的 MC 功能概况 PCa 侵袭性的预测因素和 PCa 种族差异的候选功能生物标志物；定义和 验证良性人类前列腺中存在 PCa 和 PCa 侵袭性的分子特征 活检并测试其对 PCa 差异和与 MC 关联的预测价值；并应用我们的新筛选 临床模式，取决于成功的验证研究。我们预计我们的方法可能 改善高危 PCa 的诊断和筛查，并将 MC 定位为 PCa 差异的潜在驱动因素。