Racial disparity of MIC-1 gene in prostate tumor biology

描述(由申请人提供)：癌症健康差异是美国一个主要的公共卫生问题。即使考虑到社会经济因素，少数群体的总发病率也比总体人口高，结果也比总体人口差。前列腺癌是非洲裔美国人(AA)男性发病率和死亡率高于高加索人的一种疾病。尽管社会经济因素在一定程度上可能是罪魁祸首，但人们意识到，肿瘤生物学的差异使再障男性更容易患上侵袭性前列腺癌。因此，了解生物多样性在前列腺癌中的影响对于缩小AA男性和高加索人之间观察到的癌症预后差距至关重要。我们的目标是确定巨噬细胞抑制细胞因子(MIC-1)作为一种生物因子在前列腺癌生物学中发挥关键作用，从而导致癌症健康差异。MIC-1与前列腺癌的发生发展密切相关，血清MIC-1水平升高与骨转移相关。我们实验室的初步数据清楚地表明，前列腺癌患者的血清MIC-1在AA男性明显高于高加索人。我们假设，非裔美国男性前列腺癌微环境中MIC-1水平的增加导致前列腺癌健康差距的增加。到目前为止，MIC-1在区分AA男性和高加索人侵袭性前列腺癌方面的作用还没有得到研究。为了验证上述假设，我们的具体目的是：1)确定MIC-1在非裔美国人和高加索人前列腺癌健康差异中的临床意义；2)利用小鼠模型确定MIC-1在免疫监测中导致前列腺癌差异的机制。利用多学科研究团队的技能，我们将检测前列腺癌复发转移患者和新诊断前列腺癌患者的血清MIC-1水平。我们还将分析AA男性和高加索人前列腺癌组织档案标本中MIC-1的间质和上皮表达。我们将通过利用免疫活性小鼠模型分析浸润性淋巴细胞的性质来确定MIC-1调节侵袭性前列腺癌的机制作用。显然，AA男性和患有前列腺癌的高加索人的血清MIC-1水平不同。这将对确定MIC-1在前列腺癌健康差距中的生物学作用产生重大影响，以便随后将其转化为临床，利用改进的治疗方式减少患有前列腺癌的非裔美国男性的患病人数。

DESCRIPTION (provided by applicant): Cancer health disparities represent a major public health concern in the United States. Even when socioeconomic factors are accounted for, minority populations have higher overall incidence rates and worse outcomes than the overall population. Prostate cancer is one of such disease with higher incidence and death rate in African American (AA) men than Caucasians. Although socioeconomic factors may be blamed to a certain extent, it is being appreciated that the differences in tumor biology make AA men more prone to the aggressive prostate cancer. Therefore, understanding the impact of biological variability in prostate cancer is vital to reduce the observed cancer outcome gaps between AA men and Caucasians. Our goal is to determine the role of macrophage inhibitory cytokine (MIC-1) as a biological factor that play a critical role in prostate tumor biology leading to cancer heath disparities. MIC-1 has drawn significant attention due to its increased association with the development and progression of prostate cancer, and increasing serum MIC-1 levels correlates with the presence of bone metastasis. Preliminary data from our laboratory clearly demonstrate that serum MIC-1 in prostate cancer patients is significantly higher in AA men than Caucasians. We hypothesize that increased level of MIC-1 in prostate tumor microenvironment of African American men contributes to an increase in prostate cancer health disparity. To date the role of MIC-1 to differentiate the aggressive prostate cancer among AA men and Caucasians has not been investigated. To test the above hypothesis, our specific Aims are: 1) To determine the clinical significance of MIC-1 in prostate cancer health disparity among African American men and Caucasians; and 2) To determine the mechanism of MIC-1 in immune surveillance leading to prostate cancer disparity using mouse models. Using the skills of multidisciplinary team of investigators, we will measure serum MIC-1 levels in prostate cancer patients with recurrent metastasis, and newly diagnosed prostate cancer. We will also analyze the stromal and epithelial expression of MIC-1 in archival specimens of human prostate tumor tissues from AA men and Caucasians. We will determine the mechanistic role of MIC-1 regulating aggressive prostate cancer by analyzing the nature of infiltrating lymphocytes using immuno- competent mouse models. Clearly, the serum MIC-1 levels differ in AA men and Caucasians with prostate cancer. This will have a significant impact to establish the biological role of MIC-1 contributing o prostate cancer health disparity for its subsequent translation into clinics to reduce the sufferin of African American men with prostate cancer using improved therapeutic treatment modalities.