Glycoprotein biomarkers for the early detection of aggressive prostate cancer

用于早期检测侵袭性前列腺癌的糖蛋白生物标志物

• 批准号: 8135439
• 负责人: Hui Zhang
• 金额: $ 43.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8135439
• 关键词: Biological Assay; Biological Markers; Cancer Detection; Cancer Patient; Cessation of life; Clinical; Communities; Databases; Disease; Early Detection Research Network; Early Diagnosis; Early treatment; Glycopeptides; Glycoproteins; Health Expenditures; Laboratories; Malignant Neoplasms; Malignant neoplasm of prostate; Methods; Modeling; Modification; Monitor; Operative Surgical Procedures; Patients; Performance; Polysaccharides; Prospective Studies; Prostate; Reaction; Research; Retrospective Studies; Sampling; Serum; Testing; Tissue Microarray; Tissues; Validation; base; cancer therapy; cancer type; men; novel

DESCRIPTION (provided by applicant): Prostate cancer is the most prevalent type of cancer for U.S. men (about 192,280 new cases this year), and it is the second highest contributor to cancer death among men in the U.S. (27,360 will die of it this year). A major issue in prostate cancer detection and therapy is that we currently have no method to reliably distinguish aggressive prostate cancer from non-aggressive prostate cancer using available biomarkers. This leads to significant unnecessary suffering among prostate cancer patients and leads to massive unnecessary health care expenditures. We hypothesize that specific glycoproteins and glycan modifications of glycoproteins can be used to distinguish aggressive from non-aggressive prostate cancer in tissue and serum. We propose in four specific aims to develop novel glycoprotein biomarkers that can detect aggressive cancer in primary tissues and pre-surgical serum. In Aim 1, we will analyze glycans and glycoproteins from metastatic, aggressive cancer, non-aggressive cancer, and normal prostate tissues to identify glycoproteins associated with aggressive prostate cancer. In Aim 2, we will develop highly sensitive, specific, and high throughput MS based SRM assays for the candidate glycopeptides identified from Aim 1. We will optimize the SRM assays and determine their analytical performance, and construct an SRM database and make the assay available to the research community. In Aim 3, we will use the developed SRM assays from Aim 2 to verify the glycoproteins for aggressive prostate cancer in additional prostate cancer tissues and validate these tissue glycoproteins using tissue microarrays. In Aim 4, we will use the SRM assays to determine which of the verified glycopeptides in tissues can be detected in patient's sera, and therefore can be used as serum tests. Then, we will apply the SRM assays to the serum samples and develop validate multivariate models for detecting aggressive prostate cancer using serum tests. In addition, we will validate these markers and multivariate models using an independent testing set of prostate cancer serum. If successful, the identified and validated biomarkers will be tested by EDRN biomarker reference (BRL) and clinical validation (CVC) laboratories in retrospective and prospective studies. Biomarkers capable of distinguishing aggressive from nonaggressive prostate cancer would present men with non-aggressive prostate cancer from overtreatment, and could allow men with aggressive cancer to receive appropriate treatment earlier in the course of their diseases. SRM = selected reaction monitoring

描述（由申请人提供）：前列腺癌是美国男性最常见的癌症类型（今年新增病例约 192,280 例），也是美国男性癌症死亡的第二大原因（今年将有 27,360 人死于该病）年）。前列腺癌检测和治疗的一个主要问题是，我们目前没有方法使用可用的生物标志物来可靠地区分侵袭性前列腺癌和非侵袭性前列腺癌。这导致前列腺癌患者遭受严重不必要的痛苦，并导致大量不必要的医疗保健支出。我们假设特定的糖蛋白和糖蛋白的聚糖修饰可用于区分组织和血清中的侵袭性和非侵袭性前列腺癌。我们提出了四个具体目标，即开发能够检测原发组织和术前血清中侵袭性癌症的新型糖蛋白生物标志物。在目标 1 中，我们将分析来自转移性、侵袭性癌症、非侵袭性癌症和正常前列腺组织的聚糖和糖蛋白，以识别与侵袭性前列腺癌相关的糖蛋白。在目标 2 中，我们将为目标 1 中确定的候选糖肽开发基于 MS 的高灵敏度、特异性和高通量 SRM 测定。我们将优化 SRM 测定并确定其分析性能，并构建 SRM 数据库并使该测定可用到研究界。在目标 3 中，我们将使用目标 2 中开发的 SRM 检测来验证其他前列腺癌组织中侵袭性前列腺癌的糖蛋白，并使用组织微阵列验证这些组织糖蛋白。在目标 4 中，我们将使用 SRM 检测来确定组织中哪些经过验证的糖肽可以在患者血清中检测到，因此可以用作血清检测。然后，我们将 SRM 检测应用于血清样本，并开发有效的多变量模型，用于使用血清检测检测侵袭性前列腺癌。此外，我们将使用前列腺癌血清的独立测试集来验证这些标记物和多变量模型。如果成功，已识别和验证的生物标志物将由 EDRN 生物标志物参考 (BRL) 和临床验证 (CVC) 实验室在回顾性和前瞻性研究中进行测试。能够区分侵袭性前列腺癌和非侵袭性前列腺癌的生物标志物将使患有非侵袭性前列腺癌的男性免于过度治疗，并且可以使患有侵袭性癌症的男性在病程早期接受适当的治疗。 SRM = 选择反应监测