MARKERS OF PROSTATE CANCER PROGRESSION: A TELOMERE-BASED PROTEOMIC APPROACH

前列腺癌进展的标志物：基于端粒的蛋白质组学方法

基本信息

批准号：
7960225
负责人：
MARCO BISOFFI
金额：
$ 9.65万
依托单位：
NEW MEXICO STATE UNIVERSITY LAS CRUCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7960225
关键词：
Adenocarcinoma Allelic Imbalance Area Benign Biochemical Biochemistry Biological Markers Biomedical Research Cancer Patient Cancerous Cell Adhesion Molecules Cell model Cells Clinical Computer Retrieval of Information on Scientific Projects Database Development Diagnosis Early Diagnosis Funding Genetic Genomic Instability Genomics Goals Grant Histologic Human Hyperplasia Institution Investigation LNCaP Malignant Neoplasms Malignant neoplasm of prostate Medical center Metastatic Neoplasm to the Bone Molecular Chaperones New Mexico Normal tissue morphology Patients Ploidies Prostatectomy Prostatic Diseases Prostatic Tissue Proteins Proteomics Research Research Personnel Research Project Grants Resources Sampling Signal Transduction Source Tissue Sample Tissues United States National Institutes of Health Universities Validation Veterans Xenograft procedure base medical schools novel outcome forecast protein transport telomere tumor tumor progression

项目摘要

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. The main purpose of this research project is to identify protein biomarkers for both prostate cancer development and progression. Two principal sources are used to achieve this goal. The first is the LNCaP/C4-2/C4-2B xenograft cell model for prostate cancer progression. We have previously used genomic and proteomic approaches to identify novel, previously undescribed factors involved in therapy resisitance and bone metastasis. These include proteins from different areas of cell biochemistry, including signal transduction, cell adhesion, protein transport, and chaperon function. We are currently investigating the exact function of these new factors in promoting prostate cancer. The second source consists of prostatectomy tissue samples, cancerous and matched adjacent, collected at the University New Mexico School of Medicine and the Veterans Affairs Medical Center in Albuquerque. We have so far collected samples from ~150 patients diagnosed with prostatic diseases such as adenocarcinoma and benign hyperplasia. Assessment of markers of genomic instability in these tissues, such as telomere DNA content and allelic imbalance, indicates the presence of genetic and biochemical alterations. We are using genomic and proteomic approaches to characterize these alterations and have identified a number of new leads currently under investigation for their exact function. In particular, proteins found to be altered in histologically normal tissues adjacent to tumors may be biomarkers of early cancer development. We plan to determine the clinical value of newly discovered biomarkers in validation sets of human prostatic tissues in order to develop means of earlier diagnosis and more accurate prognosis for prostate cancer patients.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目和研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。该研究项目的主要目的是确定前列腺癌发生和进展的蛋白质生物标志物。有两个主要来源用于实现这一目标。第一个是前列腺癌进展的 LNCaP/C4-2/C4-2B 异种移植细胞模型。我们之前曾使用基因组和蛋白质组学方法来识别涉及治疗抵抗和骨转移的新的、以前未描述的因素。这些包括来自细胞生物化学不同领域的蛋白质，包括信号转导、细胞粘附、蛋白质运输和伴侣功能。我们目前正在研究这些新因子在促进前列腺癌中的确切功能。第二个来源包括前列腺切除术组织样本，癌性的和匹配的邻近样本，收集于新墨西哥大学医学院和阿尔伯克基退伍军人事务医疗中心。迄今为止，我们已收集了约 150 名被诊断患有腺癌和良性增生等前列腺疾病的患者的样本。对这些组织中基因组不稳定性标记的评估，例如端粒 DNA 含量和等位基因不平衡，表明存在遗传和生化改变。我们正在使用基因组和蛋白质组学方法来表征这些改变，并确定了一些目前正在研究其确切功能的新线索。特别是，在邻近肿瘤的组织学正常组织中发现改变的蛋白质可能是早期癌症发展的生物标志物。我们计划确定新发现的生物标志物在人类前列腺组织验证集中的临床价值，以便为前列腺癌患者开发早期诊断和更准确预后的方法。