Small Integrin-binding Glycophosphoproteins as Biomarkers for Prostate Cancer

小整合素结合糖磷蛋白作为前列腺癌的生物标志物

• 批准号: 8277907
• 负责人: NEAL S FEDARKO
• 金额: $ 33.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-08 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277907
• 关键词: Activities of Daily Living; Address; Aging; Benign; Benign Prostatic Hypertrophy; Biological; Biological Markers; Biopsy; Blood; Cancer Detection; Cancerous; Caring; Case-Control Studies; Clinical; Cohort Studies; Complication; Data; Development; Diagnosis; Diagnostic; Discrimination; Disease; Disease Progression; Early Detection Research Network; Early Diagnosis; Early identification; Environment; Enzyme-Linked Immunosorbent Assay; Evaluation; Event; Functional disorder; Gene Family; Glycoproteins; Goals; Health; Health Status; Hematogenous Spread; Immune; Incidence; Individual; Indolent; Infiltration; Integrin Binding; Ligands; Link; Longitudinal Studies; Macrophage Activation; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Methods; Modeling; Monitor; Neoplasm Metastasis; Osteoporosis; Patients; Physicians; Play; Procedures; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Proteins; Quality of life; Reference Standards; Research; Risk; Role; Sampling; Screening procedure; Serum; Specimen; Speed; Staging; Statistical Methods; Study Subject; Symptoms; Testing; Time; Tooth structure; Translations; United States; Validation; Variant; Work; base; bone; cancer diagnosis; cancer initiation; case control; clinical care; cohort; digital; follow-up; head-to-head comparison; high risk; improved; innovation; member; men; mortality; multi-site trial; neoplastic cell; novel; novel marker; outcome forecast; population based; pre-clinical; prognostic; rectal; research clinical testing; response; tool; tumor growth; tumor progression

DESCRIPTION (provided by applicant): Prostate cancer (PCA), the leading cancer diagnosed among men in the United States, has a highly variable rate of progression, with indolent forms having minimal impact on functional ability and mortality while aggressive forms have high mortality. Though physical symptoms, digital rectal exam, measuring prostate-specific antigen levels, and biopsy are currently the methods of choice for detecting PCA, they are not ideal as sometimes these screening tools mistake those without disease as having disease and can not distinguish between benign and malignant disease, or slow growing versus rapidly progressing cancer. Thus PCA management requires not only improved early detection, but also the development of markers for distinct disease types as well as for predicting risk for aggressive cancer. Members of a gene family we have been studying, termed SIBLINGs (for Small Integrin Binding Ligand N-linked Glycoproteins) are normally expressed by bone but are also induced in different cancers. Initial studies indicate that SIBLINGs can be informative markers for PCA detection and that individual members correlate with different aspects of PCA initiation and progression. Because of these different pathological associations, our main hypothesis is that SIBLINGs can be developed as diagnostic and prognostic biomarkers for prostate health. An immediate objective is to provide evidence to support multi-site trials of these novel PCA biomarkers, to speed their rapid clinical evaluation. Our intermediate objective is to determine whether these proteins will enable the discrimination between different forms of prostate health/status (e.g. - normal, benign, cancerous) as well as in other cancers or diseases which share similar pathophysiology to PCA. The ultimate goal of the research is to provide new markers that either alone or in combination with existing clinical measures not only improve diagnosis, but also predict the aggressiveness of PCA so that rational treatment decisions can be made by both patients and physicians. The research approach is to use a national reference set of case-control samples for PCA, case control sets of matched samples from other disease states (e.g. - benign prostate hyperplasia, osteoporosis), and samples from a large longitudinal cohort study of aging. Central to the research is the use of samples where extensive demographic and clinical follow up data has also been collected on these subjects/samples. A sufficient number of cases (for diagnostics) and events (for prognostics) have been collected to enable a clinically meaningful testing of marker utility. SIBLINGs are measured in serum in study subjects by competitive enzyme linked immunosorbent assays and the markers are evaluated individually and in composites with other demographic and clinical parameters through appropriate and complementary statistical methods. The proposed research has the potential to validate novel serum tests that may aid accurate identification of early stage disease, reduce over treatment of slow growing disease and help identify patients with more aggressive disease requiring additional therapy.

描述（由申请人提供）：前列腺癌（PCA）是美国男性中诊断的主要癌症，其进展速度变化很大，惰性形式对功能能力和死亡率的影响最小，而侵袭性形式的死亡率很高。虽然身体症状、直肠指检、测量前列腺特异性抗原水平和活检是目前检测 PCA 的首选方法，但它们并不理想，因为有时这些筛查工具会将没有疾病的人误认为患有疾病，并且无法区分良性和恶性疾病，或缓慢生长和快速进展的癌症。因此，PCA 管理不仅需要改进早期检测，还需要开发针对不同疾病类型以及预测侵袭性癌症风险的标记物。我们一直在研究的基因家族成员，称为 SIBLING（小整合素结合配体 N 连接糖蛋白）通常由骨骼表达，但也在不同的癌症中被诱导表达。初步研究表明，SIBLING 可以作为 PCA 检测的信息标记，并且各个成员与 PCA 启动和进展的不同方面相关。由于这些不同的病理关联，我们的主要假设是 SIBLING 可以开发为前列腺健康的诊断和预后生物标志物。近期目标是提供证据支持这些新型 PCA 生物标志物的多中心试验，以加快其快速临床评估。我们的中期目标是确定这些蛋白质是否能够区分不同形式的前列腺健康/状态（例如正常、良性、癌性）以及与 PCA 具有相似病理生理学的其他癌症或疾病。该研究的最终目标是提供新的标记物，无论是单独使用还是与现有的临床测量相结合，不仅可以改善诊断，还可以预测 PCA 的侵袭性，以便患者和医生能够做出合理的治疗决策。研究方法是使用 PCA 病例对照样本的国家参考集、来自其他疾病状态（例如良性前列腺增生、骨质疏松症）的匹配样本的病例对照集，以及来自大型老龄化纵向队列研究的样本。研究的核心是样本的使用，其中还收集了有关这些受试者/样本的广泛人口统计和临床随访数据。已经收集了足够数量的病例（用于诊断）和事件（用于预后），以便能够对标记物效用进行具有临床意义的测试。通过竞争性酶联免疫吸附测定来测量研究对象血清中的同胞兄弟姐妹，并通过适当和互补的统计方法单独评估标记物并与其他人口统计和临床参数进行综合评估。拟议的研究有可能验证新颖的血清测试，这可能有助于准确识别早期疾病，减少对缓慢生长的疾病的过度治疗，并帮助识别患有需要额外治疗的更具侵袭性疾病的患者。