A Systematic Approach to Early Diagnosis of Cancer

描述（由申请人提供）：前列腺癌是第二大 癌症是男性死亡的主要原因，每年约有32，000人死于癌症。一个 迫切需要改进诊断和预后工具。PSA测试 广泛使用的诊断工具，但它们产生了不可接受的程度的错误 阳性和假阴性。由于缺乏预测工具，许多男性 接受不必要的激进治疗我们在此描述了一个系统的 发现分泌性前列腺肿瘤生物标志物的计划。在第一阶段，我们 开发了一个？分泌物陷阱？，一种用于快速分离的文库的方案， 来自任何来源的分泌序列标签。从一个？被困住了图书馆标识 可接近的蛋白质，例如细胞表面和细胞外蛋白质，它是一种 发现具有诊断和预后功能的生物标志物的有力手段 潜力我们将从前列腺中产生一个分泌序列标签库， 我们将选择100个符合基本标准的肿瘤， 生物标志物。我们将确定候选标记的表达谱 通过自动化，高通量原位杂交和免疫组织化学。 最后，我们将确定这些生物标志物中的任何一种是否存在于 前列腺癌患者的血清。这些实验将确定 可以作为诊断或预后指标商业化的生物标志物。

DESCRIPTION (provided by applicant): Prostate cancer is the second leading cause of cancer death in men, killing approximately 32,000 men annually. An urgent need exists for improved diagnostic and prognostic tools. PSA tests are widely used diagnostic tools, but they yield an unacceptable degree of false positives and false negatives. Due to a lack of prognostic tools, many men undergo unnecessary, radical treatments. We describe herein a systematic program for the discovery of secreted prostate tumor biomarkers. In Phase I, we developed a ?secretion trap?, a protocol for rapid isolation of a library of secreted sequence tags from any source. Since a ?trapped? library identifies accessible proteins, e.g. cell surface and extracellular proteins, it is a powerful means for discovering biomarkers with diagnostic and prognostic potential. We will generate a library of secreted sequence tags from prostate tumors and we will choose 100 that fulfill basic criteria required of useful biomarkers. We will determine the expression profiles of the candidate markers by automated, high-throughput in situ hybridization and immunohistochemistry. Finally, we will determine whether any of these biomarkers are present in the serum of patients with prostate cancer. These experiments will identify biomarkers that may be commercialized as diagnostic or prognostic indicators.