CHARACTERIZATION OF EARLY STAGE PROSTATE CANCER

早期前列腺癌的特征

• 批准号: 6377560
• 负责人: DAN MERCOLA
• 金额: $ 119.43万
• 依托单位: SIDNEY KIMMEL CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6377560
• 关键词: clinical research; cooperative study; gene expression; genetic markers; genetic techniques; human subject; neoplasm /cancer classification /staging; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction; prostate neoplasms

This proposal will define a molecular classification schema for organ-confined prostate cancer. The schema will be based on patterns of gene expression and DNA methylation found within prostate tumors and the surrounding stroma. The aim of the project is to create a method for classifying such tumors based on tumor biology rather than simply on histology. The development of a classification schema based on molecular profiles would improve our ability to treat and manage organ-confined prostate cancer. Four complementary approaches to the generation of molecular profiles will be used. Gene expression molecular profiles will be generated using 1) Affymetrix Gene Chip technology and 2) RNA arbitrarily primed (RAP-PCR) based cDNA array analysis. DNA methylation molecular profiles of will be generated using 1) methylation-sensitive array analysis and 2) restriction landmark genomic scanning (RLGS). The utility and complementarity of each approach in relation to the others will be evaluated. Prospective clinical data will be collected to allow for the correlation of each molecular profile with important tumor characteristics. With the completion of this project we expect that we will have: Defined a molecular profile for organ-confined prostate cancer that will supplant the standard pathologic diagnosis and staging of these tumors. Defined additional profiles that correlate with important clinical characteristics in these patients. Such characteristics should include both important pathologic parameters (i.e. Gleason score, PSA levels, stage), and clinical outcome (likelihood of metastatic disease, likelihood of hormonal, radiation or chemotherapy response, time to progression and survival). Discovering molecular profiles within prostate tumors that prognosticate for patient outcome will greatly improve the quality of life for these patients.

该提案将为器官局限性前列腺癌定义分子分类方案。 该方案将基于前列腺肿瘤和周围基质中发现的基因表达和 DNA 甲基化模式。 该项目的目的是创建一种基于肿瘤生物学而不是简单地基于组织学对此类肿瘤进行分类的方法。 基于分子谱的分类方案的开发将提高我们治疗和管理器官局限性前列腺癌的能力。将使用四种互补方法来生成分子谱。 将使用 1) Affymetrix 基因芯片技术和 2) 基于 RNA 任意引物 (RAP-PCR) 的 cDNA 阵列分析来生成基因表达分子谱。 DNA 甲基化分子谱将使用 1) 甲基化敏感阵列分析和 2) 限制性标志基因组扫描 (RLGS) 生成。 将评估每种方法相对于其他方法的实用性和互补性。将收集前瞻性临床数据，以便将每个分子谱与重要的肿瘤特征相关联。随着该项目的完成，我们预计我们将： 定义器官局限性前列腺癌的分子谱，它将取代这些肿瘤的标准病理诊断和分期。 定义了与这些患者的重要临床特征相关的其他特征。 这些特征应包括重要的病理参数（即格里森评分、PSA水平、分期）和临床结果（转移性疾病的可能性、激素、放疗或化疗反应的可能性、进展时间和生存）。发现前列腺肿瘤内可预测患者预后的分子谱将大大改善这些患者的生活质量。