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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 目前用于筛查和风险评估前列腺癌的技术，是手术活检程序的先决条件，基于对单个血清生物标志物的测量，或在循环恶性细胞中单个基因的表达。 这些技术具有许多局限性，包括缺乏诊断的特异性和准确性，也缺乏预后信息。 这最终产生了大量的假阳性诊断，因此不必要地进行了大量的手术活检。 越来越多的证据表明，患有前列腺癌和其他形式的恶性疾病的个体表现出免疫反应，可以在周围血液中循环的白细胞中改变基因表达的水平检测到。 在许多单个基因的白细胞中对mRNA转录物的定量已经证明了基因表达水平与肿瘤的存在之间的关联。 已经表明，单个蛋白质的血清水平与白细胞中的差异基因表达相关，并提供了一些有关肿瘤阶段的信息。此外，与多个基因的健康对照相比，我们已经开始了一项试点研究，以检查非裔美国人患有前列腺癌的男性的基因表达水平，并显示了多个基因的表达差异。 假设：这些观察构成了这项拟议研究的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源自前列腺癌患者和对照组的血液中循环白细胞中转录的14,000个基因的表达水平。 利用这项技术，我们建议研究以下假设：患有前列腺癌的个体在其外周血清细胞中表现出基因表达水平的保守模式或签名，这与控制受试者的白细胞中相应的表达模式不同。 我们将进一步测试以下假设：在不同组织学等级处患有前列腺肿瘤的癌症患者将产生不同的表达特征，反映了肿瘤的生物学阶段和攻击性，因此可以用来在不同病理阶段分化肿瘤。 整个建议的具体目的是： 具体目标： a）在该项目的两年中，从40名前列腺癌患者和20名健康对照组的血清细胞收集血清细胞。 b）采用Affymetrix Genechip微阵列技术来测量白细胞样品中的全球基因表达。 c）采用数据分析算法来建立白细胞多基因表达特征，可以区分前列腺癌患者和对照组。 特定目的两个：利用特定目标生成的表达数据，允许将前列腺癌患者分为与前列腺肿瘤进展的特定阶段相对应的组。 该提议的最终目标。 这里提出的研究的最终目标是开发一种新技术，该技术不需要侵入性手术，但可以准确诊断前列腺癌，并提供有关肿瘤阶段和生物学侵略性的详细预后信息。 该项目的成功将产生一种急需的，无创的工具，用于对疾病的前列腺癌进行特定于阶段的诊断，因此是鉴定患有前列腺肿瘤男性的重要屏幕。