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

基本信息

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
项目类别：
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

项目摘要

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）：在美国男性中诊断出的主要癌症的前列腺癌（PCA）的进展速度差异很大，而懒惰的形式对功能能力和死亡率的影响最小，而侵略性形式的死亡率很高。尽管身体症状，数字直肠检查，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错误地误认为那些没有疾病的人是患有疾病，并且无法区分良性和恶性病，或者较慢而增长速度迅速而发展。因此，PCA管理不仅需要改善早期检测，而且还需要开发不同疾病类型的标志物以及预测侵袭性癌症的风险。我们一直在研究的基因家族的成员，称为兄弟姐妹（用于小型整合素结合配体N-连接糖蛋白）通常由骨骼表达，但也会在不同的癌症中诱导。最初的研究表明，兄弟姐妹可以是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，我们的主要假设是兄弟姐妹可以作为前列腺健康的诊断和预后生物标志物发展。一个直接的目标是提供证据，以支持这些新型PCA生物标志物的多站点试验，以加快其快速临床评估。我们的中间目标是确定这些蛋白质是否能够歧视不同形式的前列腺健康/状态（例如 - 正常，良性，癌症），以及其他癌症或与PCA相似的病理生理学的癌症或疾病。该研究的最终目的是提供新的标记，即单独或与现有的临床措施结合使用，不仅可以改善诊断，而且还可以预测PCA的侵略性，以便患者和医生都可以做出合理的治疗决策。研究方法是使用全国参考病例对照样本进行PCA，来自其他疾病状态的匹配样本（例如 - 良性前列腺增生，骨质疏松症）的案例控制，以及来自大型敏捷纵向同伴研究的样品。该研究的核心是使用样本，其中还收集了有关这些受试者/样本的广泛人口和临床随访数据。已经收集了足够数量的病例（用于诊断）和事件（用于预后），以实现对标记实用程序的临床意义测试。通过竞争性酶连接的免疫吸附测定法在血清中测量兄弟姐妹，并通过适当和互补的统计方法对标记进行单独和具有其他人口统计学和临床参数的复合材料评估。拟议的研究具有验证新型血清测试的潜力，可以帮助准确鉴定早期疾病，减少过度治疗缓慢的疾病，并有助于鉴定患有更侵略性疾病的患者需要额外的治疗。