SELDI-TOF Analysis of Prostate Cancer Proteins in Sera of Hispanic Patients-pilot

西班牙裔患者血清中前列腺癌蛋白的 SELDI-TOF 分析 - 试点

• 批准号: 7122380
• 负责人: MARGARITA IRIZARRY-RAMIREZ
• 金额: $ 3.5万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7122380
• 关键词: Hispanic Americans; clinical research; genetic markers; human subject; male; mass spectrometry; neoplasm /cancer classification /staging; neoplastic process; prostate neoplasms; proteomics; racial /ethnic difference; serum

Prostate cancer (PCa) is the second leading cause of cancer related deaths among males in the United States. Hispanic patients seem to have a lower five year relative survival rate regardless of the stage of disease than white non Hispanic. The long term goal is to identify new molecular markers related to progression of the disease. Current tumor markers in use in the clinical setting have been shown to have low specificity and low predictive value. New technologies for the analysis of the proteome and current technologies for the analysis of the genome of the prostate gland open a new window for identifying proteins and their genes that may selectively express during the early and late stages of prostate (PCa). Recently some studies have suggested distinct protein patterns expressed in the serum of Caucasian and African-American prostate cancer patients. No broad study has been done in a population with a strong Hispanic imheritance. We hypothesize that distinct proteome expression underlies the difference in stage progression and survival in the Hispanic population. In the proposed research a proteomics approach will be used in the examination of healthy and prostate cancer Hispanic patients in Puerto Rico. Our first aim is to establish protein patterns in the sera of these patients at the time of diagnosis and before any treatment. The methodology will incorporate the use of Surface Enhanced Laser Desorption Ionization (SELDI) to compare the patterns of protein expression in healthy patients and in newly diagnosed untreated PCa patients and compare them with published results for other ethnic populations. Protein patterns for 15 healthy and 20 PCa patients will be analyzed at baseline. Patterns found will be tested for their predictive value using an additional 25 blinded samples. Our second aim is the characterization of abundant protein species with altered expression in prostate cancer using gel proteolysis and protein sequencing and isoelectric focusing. In aim three we will correlate changes in protein patterns with stages of progression of the disease. Sera sample analysis will be performed through years 1-4 of this project to assay for changes in pattern that may correlate to progression. In the context of this project, results from these correlations may serve as the base for a broader study to find predictive markers to assign patients to specific therapies. This research will provide further understanding of the changes underlying the development of prostate cancer in Hispanics. This project will also provide the opportunity to increase the number of ethnic minority, trained clinical researchers and facilitate the recruitment of Hispanies into clinical research.

前列腺癌（PCa）是美国男性癌症相关死亡的第二大原因。无论疾病分期如何，西班牙裔患者的5年相对生存率似乎低于非西班牙裔的白色人。长期目标是确定与疾病进展相关的新分子标志物。目前在临床环境中使用的肿瘤标志物已被证明具有低特异性和低预测价值。的新技术 蛋白质组的分析和目前用于前列腺基因组分析的技术为鉴定可能在前列腺（PCa）早期和晚期期间选择性表达的蛋白质及其基因打开了新的窗口。最近的一些研究表明，在高加索人和非洲裔美国人的血清中表达不同的蛋白质模式， 前列腺癌患者。没有广泛的研究已经在一个人口与一个强大的西班牙裔imheritance。我们假设不同的蛋白质组表达是西班牙裔人群中阶段进展和生存差异的基础。在拟议的研究中，蛋白质组学方法将用于检查波多黎各的健康和前列腺癌西班牙裔患者。我们的第一个目标是在诊断时和任何治疗前建立这些患者血清中的蛋白质模式。该方法将包括使用Surface 增强激光解吸电离（SELDI），比较健康患者和新诊断的未经治疗的PCa患者的蛋白质表达模式，并将其与其他种族人群的已发表结果进行比较。将在基线时分析15例健康患者和20例PCa患者的蛋白质模式。发现的模式将被测试其预测性 使用额外的25个盲法样本计算值。我们的第二个目标是使用凝胶蛋白水解和蛋白质测序以及等电聚焦来表征前列腺癌中表达改变的丰富蛋白质种类。在第三个目标中，我们将把蛋白质模式的变化与疾病的进展阶段联系起来。将在本项目的第1-4年进行血清样本分析，以测定可能与进展相关的模式变化。在 在这个项目的背景下，这些相关性的结果可以作为更广泛的研究的基础，以找到预测性标志物来为患者分配特定的治疗。这项研究将进一步了解西班牙裔前列腺癌发展的潜在变化。该项目还将提供机会，以增加少数民族的数量，训练有素的临床研究人员，并促进招聘西班牙人进入临床 research.