Identification of Prostate Cancer Stage in Hispanics Using Serum Protein Profile

描述（由申请人提供）：前列腺癌是男性癌症相关死亡的第二大原因。西班牙裔人口受这种疾病的影响，与非西班牙裔白人相比，他们的五年生存率较低，尽管比非裔美国男性好一些。目前在临床环境中使用的肿瘤标志物已被证明具有低特异性和阳性预测价值。最近一些研究表明，在白种人、非裔美国人和亚裔前列腺癌患者的血清中表达了不同的蛋白质模式。目前还没有针对西班牙裔遗传较强的人群进行的研究。长期目标是确定与西班牙裔前列腺癌（Pac）进展相关的分子标志物及其对治疗的反应。本研究的目的是评估西班牙裔人群中Pac的蛋白质模式。中心假设是前列腺蛋白质组表达随着疾病的进展阶段而变化，因此不同蛋白质组模式的出现可能作为前列腺肿瘤进展的预测因子，并有助于解释该人群中Pac的特征。该方法将结合使用表面增强激光解吸分离（SELDI-TOF）和蛋白质电聚焦来比较健康患者和新诊断的未经治疗的前列腺癌患者的蛋白质表达模式。我们的第一个具体目标是确定波多黎各新诊断的西班牙裔前列腺癌患者血清中的蛋白质模式。由于在这些西班牙裔患者中出现的特征蛋白在其他人群中不存在或未被描述，可能解释了该人群中PCA特征的差异，我们的第二个目标是选择和表征可能对理解潜在的分子机制和生理意义至关重要的独特蛋白。最后，我们的第三个目标是将蛋白质模式与疾病的进展和治疗类型联系起来，在这个项目的背景下，这些相关性的结果可以作为一个更广泛的研究的基础，以找到预测标记，为患者分配特定的治疗。这项工作的基本原理是，疾病的早期标记和癌症阶段进展标记的识别最终将转化为西班牙裔人群更好的诊断和生存率，并且这些标记可能具有普遍性。有了表征组成不同谱图的蛋白质的能力，就有可能研究它们在疾病生理学中的可能作用。这一知识将大大提高靶向这些蛋白质的能力，以开发新疗法或更好地利用现有疗法，从而提高生存率。

DESCRIPTION (provided by applicant): Prostate cancer is the second leading cause of cancer related death among males. The Hispanic population is affected by the disease, and their five year survival rates are lower when compared to the white non Hispanic population although somewhat better than for the African-American males. Current tumor markers in use in the clinical setting have been shown to have low specificity and positive predictive value. Recently some studies have suggested distinct protein patterns expressed in the serum of Caucasian and African-American and Asian prostate cancer patients. No study has been done in a population with a strong Hispanic inheritance. The long term goal is to identify molecular markers related to prostate cancer (Pac) progression in Hispanics and to their response to therapy. The objective of this study is to evaluate protein patterns of Pac in a Hispanic population. The central hypothesis is that prostate gland proteome expression, changes through progression stages of the disease, therefore the onset of distinct proteomic patterns may serve as a predictor of tumor progression in the prostate gland and help to explain the characteristics of Pac In this population. The methodology will incorporate the use of Surface Enhanced Laser Desorption lonization (SELDI-TOF) and protein electro focusing to compare the patterns of protein expression in healthy patients and in newly diagnosed untreated prostate cancer patients. Our first specific aim is to identify a protein pattern in the sera of newly diagnosed Hispanic prostate cancer patients in Puerto Rico. Since signature protein(s) that appear in these Hispanic patients and that are absent or not described in other populations, may account for the difference PCA characteristics in this population, our second aim is to select and characterize distinct protein(s) that may be crucial to the understanding of the underlying molecular mechanisms and physiological significance. Finally our third aim is to correlate protein patterns with progression of the disease and type of treatment, in the context of this project, results from these correlations may serve as the base for a broader study to find predictive markers to assign patients to specific therapies. The rationale for this work is that the identification of early markers of disease and of markers for cancer stage progression will eventually translate into better diagnosis and survival rate for the Hispanic population and that these markers may acquire generalizability. With the capability of characterizing the protein(s) that composes the different profiles, it will be possible to study their possible role in the physiology of the disease. This knowledge will significantly enhance the capacity to target these proteins for the development of new therapies or a better use of current therapies, thus improving survival.