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

• 批准号: 7610361
• 负责人: MARCO BISOFFI
• 金额: $ 5.36万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610361
• 关键词: Adenocarcinoma; Affect; Allelic Imbalance; Androgens; Area; Benign; Biochemistry; Biological Markers; Cell Adhesion; Cell model; Cells; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Disease Progression; Epithelial; Functional disorder; Funding; Genome Stability; Genomic Instability; Genomics; Goals; Grant; Hyperplasia; Institution; Investigation; LNCaP; Lead; MAPK13 gene; Malignant neoplasm of prostate; Mass Spectrum Analysis; Measures; Medical center; Metastatic Neoplasm to the Bone; Molecular; New Mexico; Organoids; Patients; Population; Prostate; Prostatectomy; Prostatic Diseases; Prostatic Tissue; Proteins; Proteomics; Purpose; Relative (related person); Research; Research Personnel; Research Project Grants; Resources; Sampling; Signal Transduction; Source; Staging; Stromal Cells; Technology; Tissue Microarray; Tissues; United States National Institutes of Health; Universities; Validation; Veterans; Xenograft procedure; base; glucose metabolism; human tissue; medical schools; novel; prognostic; protein expression; protein transport; telomere; 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. The main purpose of this research project is to identify protein biomarkers for prostate cancer progression using the relative quantitative iTRAQTM mass spectrometry proteomic technology. Two principal sources are used to achieve this goal: (i) The LNCaP/C4-2 xenograft cell model for prostate cancer progression, and (ii) epithelial and stromal cells freshly isolated from prostatectomy samples collected at the University New Mexico School of Medicine and the Veterans Affairs Medical Center in Albuquerque. Genomic and proteomic characterization of the LNCaP/C4-2 cell model has shown that it can be used to elucidate the molecular mechanisms underlying androgen independence and bone metastasis. These investigations have resulted in the identification of novel proteins that have not been involved in prostate cancer before. These include proteins from different areas of cell biochemistry, including signal transduction (TRB2, SAPK4), cell adhesion (DSC2, DSG2), protein transport (RME-8), and glucose metabolism (mPEPCK). The expression of these proteins is currently being analyzed in tissue sections of human prostate cancer to further validate their potential use as biomarkers for progression. We have also so far collected 28 prostatectomy samples from patients diagnosed with prostatic diseases such as adenocarcinomas and benign hyperplasia. These samples resulted in 71 primary short-term cultures consisting of enriched populations of epithelial or stromal cells, or mixed organoid cultures. These samples are currently being stratified according to their level of genomic instability as measured by the extent of telomere dysfunction and allelic imbalance, two markers of genomic stability previously shown to be associated with prostatic disease progression. Subsequent proteomic analysis of samples affected by low versus high genomic instability will lead to the identification of proteins with potential prognostic value. Validation of such potential markers will be performed on human tissue arrays featuring sections of prostatic tissues of different grade and stage, as well as of metastatic origin.

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。子项目及 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利用相对定量 iTRAQTM 质谱蛋白质组学技术来鉴定前列腺癌进展的蛋白质生物标志物。用于实现这一目标的两个主要来源：(i) 用于前列腺癌进展的 LNCaP/C4-2 异种移植细胞模型，以及 (ii) 从新墨西哥大学医学院收集的前列腺切除样本中新鲜分离的上皮细胞和基质细胞阿尔伯克基退伍军人事务医疗中心。 LNCaP/C4-2 细胞模型的基因组和蛋白质组表征表明，它可用于阐明雄激素独立性和骨转移的分子机制。这些研究导致了以前未涉及前列腺癌的新蛋白质的鉴定。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（TRB2、SAPK4）、细胞粘附（DSC2、DSG2）、蛋白质转运（RME-8）和葡萄糖代谢（mPEPCK）。目前正在人类前列腺癌的组织切片中分析这些蛋白质的表达，以进一步验证它们作为进展生物标志物的潜在用途。迄今为止，我们还收集了28例被诊断患有腺癌和良性增生等前列腺疾病的患者的前列腺切除样本。这些样本产生了 71 个由富集的上皮细胞或基质细胞群体或混合类器官培养物组成的原代短期培养物。目前，这些样本正在根据基因组不稳定性水平进行分层，基因组不稳定性水平是通过端粒功能障碍和等位基因失衡的程度来衡量的，这两个基因组稳定性的标志先前被证明与前列腺疾病进展相关。随后对受低基因组不稳定性和高基因组不稳定性影响的样品进行蛋白质组学分析，将鉴定具有潜在预后价值的蛋白质。这些潜在标记的验证将在人体组织阵列上进行，该阵列具有不同级别和阶段以及转移起源的前列腺组织切片。