PROSTATE TUMOR DIAGNOSIS: BLOOD CELL MULTIGENE SIGNATURES

前列腺肿瘤诊断：血细胞多基因特征

• 批准号: 7605328
• 负责人: CATHERINE L CLELLAND
• 金额: $ 0.73万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605328
• 关键词: African American; Algorithms; Biological; Biological Markers; Biopsy; Blood; Blood Cells; Cancer Patient; Classification; Computer Retrieval of Information on Scientific Projects Database; Data; Data Analyses; Diagnosis; Diagnostic Neoplasm Staging; Disease; Exhibits; Experimental Designs; Funding; Gene Expression; Gene Expression Profile; Genes; Goals; Grant; Immune response; Individual; Institution; Invasive; Leukocytes; Malignant - descriptor; Malignant neoplasm of prostate; Measurement; Measures; Messenger RNA; Microarray Analysis; Molecular Profiling; Numbers; Operative Surgical Procedures; Pathological Staging; Pattern; Pilot Projects; Procedures; Prostatic Neoplasms; Proteins; Research; Research Personnel; Resources; Risk Assessment; Sampling; Screening procedure; Serum; Source; Specificity; Staging; Techniques; Technology; Testing; Tissue-Specific Gene Expression; Transcript; Tumor stage; United States National Institutes of Health; base; cancer cell; men; novel; peripheral blood; prognostic; success; tool; tumor; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Current techniques for the screening and risk assessment of prostate cancer, as a prerequisite to surgical biopsy procedures, are based upon the measurement of either individual serum biomarkers, or expression of individual genes in circulating malignant cells. These techniques possess a number of limitations, including lack of specificity and accuracy in the diagnosis and, also a lack of prognostic information. This ultimately yields high numbers of false positive diagnoses, and consequently unnecessarily large numbers of surgical biopsies. There is growing evidence that individuals with prostate cancer and other forms of malignant disease, exhibit immune responses that can be detected at the level of altered gene expression in leukocytes circulating in peripheral blood. Quantitation of the mRNA transcripts in leukocytes of a number of individual genes has demonstrated associations between gene expression levels and the presence of a tumor. It has been shown that serum levels of individual proteins exhibit a degree of correlation with differential gene expression in leukocytes, and provides some information on tumor stage. Additionally, we have initiated a pilot study to examine gene expression levels in African-American men with prostate cancer, and have shown expression difference for multiple genes, compared to healthy controls of multiple genes. Hypothesis: These observations form the basis of the hypothesis and experimental design of this proposed study. The use of microarray technology will allow us to measure simultaneously the expression levels of up to 14,000 genes transcribed in circulating leukocytes derived from the blood of prostate cancer patients and control individuals. With this technology, we propose to investigate the hypothesis that individuals suffering from prostate cancer exhibit a conserved pattern, or signature, of gene expression levels in their peripheral blood leukocytes, which is distinct from the corresponding pattern of expression in leukocytes from control subjects. We will test the further hypothesis that cancer patients with prostate tumors at different histological grades, will yield distinct expression signatures that reflect the biological stage and aggressiveness of the tumor, and that can thus be employed to differentiate among tumors at different pathological stages. The Specific aims of this entire proposal are to: Specific Aim One: a) Collect Blood Leukocytes from 40 Prostate Cancer Patients and 20 Healthy Control Subjects Over the Two Year Period of This Project. b) Employ Affymetrix GeneChip Microarray Technology to Measure Global Gene Expression in the Leukocyte Samples. c) Employ Data Analysis Algorithms to Establish Leukocyte Multigene Expression Signatures that Can Distinguish Between Prostate Cancer Patients and Control Subjects. Specific Aim Two: Utilize the Expression Data Generated Under Specific Aim One, to Permit Classification of Prostate Cancer Patients into Groups Corresponding to Specific Stages of Prostate Tumor Progression. Ultimate Goal of this Proposal. The ultimate goal of the research proposed here is to develop a novel technique that does not require invasive surgery, yet provides an accurate diagnosis of prostate cancer, and also provides detailed prognostic information on the stage and biological aggressiveness of the tumor. The success of this project would yield a much needed, non-invasive tool for stage-specific diagnosis of prostate cancer of the disease, and thus serve as an important pre-screen to identify men with prostate tumors.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前用于前列腺癌筛查和风险评估的技术，作为外科活检程序的先决条件，是基于单个血清生物标记物的测量，或者是循环中恶性细胞中单个基因的表达。这些技术有许多局限性，包括缺乏诊断的特异性和准确性，以及缺乏预后信息。这最终会产生大量的假阳性诊断，并因此产生不必要的大量手术活检。 越来越多的证据表明，前列腺癌和其他形式的恶性疾病患者表现出免疫反应，这种反应可以在外周血液中循环的白细胞基因表达改变的水平上检测到。对白细胞中一些单独基因的mRNA转录本的定量检测表明，基因表达水平与肿瘤的存在之间存在关联。已有研究表明，血清单个蛋白水平与白细胞差异基因表达有一定程度的相关性，并可为肿瘤分期提供一定的信息。此外，我们已经启动了一项初步研究，以检查患有前列腺癌的非裔美国人男性的基因表达水平，并显示出与多基因健康对照相比，多基因的表达差异。 假设：这些观察结果构成了本研究假设和实验设计的基础。微阵列技术的使用将使我们能够同时测量前列腺癌患者和对照组血液中循环白细胞转录的多达14,000个基因的表达水平。利用这项技术，我们提出了一种假设，即前列腺癌患者外周血白细胞中的基因表达水平显示出一种保守的模式或特征，这与对照对象的白细胞中相应的表达模式不同。我们将测试进一步的假设，即癌症患者在不同组织学级别的前列腺癌患者将产生反映肿瘤生物学阶段和侵袭性的不同表达特征，从而可以用于区分不同病理阶段的肿瘤。 整个建议的具体目的是： 具体目标一： A)在本项目的两年期间采集40名前列腺癌患者和20名健康对照组的血白细胞。 B)使用Affymetrix基因芯片微阵列技术测量白细胞样本中的全球基因表达。 C)使用数据分析算法建立可区分前列腺癌患者和对照受试者的白细胞多基因表达特征。 具体目标二：利用特定目标一下产生的表达数据，将前列腺癌患者分为与前列腺癌进展的特定阶段相对应的组。 这项提议的最终目标。 这项研究的最终目标是开发一种新的技术，这种技术不需要侵入性手术，但可以提供前列腺癌的准确诊断，并提供关于肿瘤分期和生物学侵袭性的详细预后信息。该项目的成功将为前列腺癌的分期诊断提供一种急需的、非侵入性的工具，从而成为识别患有前列腺癌的男性的重要预筛查。