Identification of Prostate Cancer Stage in Hispanics Using Serum Protein Profile

描述(申请人提供)：前列腺癌是男性癌症相关死亡的第二大原因。西班牙裔人口受到这种疾病的影响，与非西班牙裔白人人口相比，他们的五年存活率较低，尽管略好于非裔美国男性。目前临床上使用的肿瘤标记物的特异性和阳性预测值都很低。最近，一些研究表明，高加索人、非裔美国人和亚洲前列腺癌患者的血清中表达了不同的蛋白质模式。在一个西班牙裔遗传很强的人群中，还没有进行过任何研究。长期目标是确定与拉美裔前列腺癌(Pac)进展相关的分子标志物以及他们对治疗的反应。这项研究的目的是评估西班牙裔人群中Pac的蛋白质模式。中心假说是前列腺蛋白质组的表达随着疾病进展阶段的变化而变化，因此，不同蛋白质组模式的出现可能作为前列腺癌进展的预测因子，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电离(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。由于在这些拉美裔患者中出现的签名蛋白(S)以及在其他人群中缺失或未描述的签名蛋白可能解释了该人群中不同的前列腺癌特征，因此我们的第二个目标是选择并鉴定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(S)。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相关联，在这个项目的背景下，这些相关性的结果可以作为更广泛的研究的基础，以找到预测标记来将患者分配到特定的治疗方案。这项工作的基本原理是，确定疾病的早期标志物和癌症分期进展的标志物最终将转化为拉美裔人口更好的诊断和存活率，并且这些标志物可能具有普遍性。有了表征组成不同图谱的蛋白质(S)的能力，就有可能研究它们在疾病生理中的可能作用。这一知识将显著提高针对这些蛋白质的能力，以开发新的疗法或更好地利用现有疗法，从而提高存活率。

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.