Biomarkers for prostate cancer risk assessment

前列腺癌风险评估的生物标志物

• 批准号: 7108892
• 负责人: SRINIVASA R NAGALLA
• 金额: $ 10.64万
• 依托单位: PROTEOGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7108892
• 关键词: androgens; antibody; biomarker; biopsy; cancer risk; diagnosis; genes; neoplasm /cancer; prostate neoplasms; serum

DESCRIPTION (provided by applicant): Prostate cancer (CaP) is the most common malignancy in U.S. males, with over 300,000 new cases per year and almost 50,000 deaths per year. Identification of novel diagnostic markers and therapeutic targets for both incident and advanced CaP is a major goal of current research. First introduced in 1987, the serum level of prostate-specific antigen (PSA) remains the standard for non-invasive prostate cancer screening, with a level of 4.0 ng/ml being the currently accepted cut-off for referral for biopsy. A main source of concern with PSA measurements per se is the sensitivity of PSA assays versus their specificity, i.e., increased PSA levels that are due to factors other than prostate cancer, such as benign prostatic hyperplasia (BPH), prostatitis, etc. This is reflected by the fact that the ability of PSA to distinguish benign from malignant conditions is substantially better at concentrations above 10 ng/ml. Thus, the accurate characterization of cancer risk in patients in the so-called "gray zone" of 4-10 ng/ml requires an improved screening tool to prevent unnecessary diagnostic procedures. This need is reinforced by the presence of disseminated disease in 30% of men with PSA values in this range. An alternative approach would be the development of a multiplex assay that would measure a defined set of serum analytes that, together, would provide the basis for a robust algorithm for assessing CaP risk with single serum samples. We have initiated such an approach by identifying genes encoding secreted proteins that are uniquely up-regulated in CaP. We propose that the products of these genes will be present at elevated levels in the serum of men with CaP, and that these proteins represent a set of candidate biomarkers that can be exploited for the development of a sensitive and specific CaP screening tool. We will address this hypothesis in 2 specific aims. Aim 1 will determine the normal variation in an initial set of 20 candidate CaP biomarkers using antibody arrays and ELISA assays. Aim 2 will use a larger cohort that includes high-PSA, biopsy-positive and negative samples in an unblinded study to assess the efficacy of a smaller biomarker set to distinguish normals and biopsy- negative from CaP samples. These studies will provide the foundation for Phase-ll validation in a larger sample set and the identification of markers associated with disseminated, metastatic and androgen- independent disease, the improved diagnosis of which would also be of significant clinical utility.

描述（由申请人提供）：前列腺癌（CaP）是美国男性中最常见的恶性肿瘤，每年新发病例超过30万例，每年死亡近5万例。鉴定新的诊断标志物和治疗靶点的事件和先进的CaP是当前研究的主要目标。前列腺特异性抗原（PSA）的血清水平于1987年首次引入，目前仍是非侵入性前列腺癌筛查的标准，4.0 ng/ml的水平是目前接受的转介活检的截止值。与PSA测量本身相关的主要来源是PSA测定的灵敏度相对于其特异性，即，由于前列腺癌以外的因素，如良性前列腺增生（BPH）、前列腺炎等，导致PSA水平升高。这反映在PSA区分良性和恶性疾病的能力在浓度高于10 ng/ml时明显更好。因此，在4 - 10 ng/ml的所谓"灰色区域"中准确表征患者的癌症风险需要改进的筛查工具以防止不必要的诊断程序。PSA值在此范围内的男性中有30%存在播散性疾病，这一需求得到了加强。另一种方法是开发一种多重测定法，该测定法将测量一组定义的血清分析物，这些血清分析物一起为使用单一血清样本评估CaP风险的稳健算法提供基础。我们已经启动了这样一种方法，通过鉴定编码分泌蛋白的基因，这些蛋白在CaP中独特地上调。我们建议，这些基因的产物将在升高的水平存在于男性血清中的钙磷，这些蛋白质代表了一组候选的生物标志物，可以利用开发一个敏感和特异性的钙磷筛选工具。我们将在两个具体目标中解决这个假设。目标1将使用抗体阵列和ELISA测定法确定初始组的20个候选CaP生物标志物中的正常变化。目标2将在非盲研究中使用包括高PSA、活检阳性和阴性样本的较大队列，以评估较小生物标志物集区分正常和活检阴性与CaP样本的功效。这些研究将为在更大的样本集中进行II期验证和鉴定与播散性、转移性和雄激素非依赖性疾病相关的标志物提供基础，其改进的诊断也将具有显著的临床实用性。