Ye Fei, Han Xiaoxia, Shao Yonzhao, Lo Jingzhi, Zhang Fengxia, Wang Jinhua, Melamed Jonathan, Deng Fang-Ming, Sfanos Karen S, De Marzo Angelo, Ren Guoping, Wang Dongwen, Zhang David, Lee Peng
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center New York, USA.
Department of Biostatstics, New York University School of Medicine New York, USA.
Am J Cancer Res. 2022 Apr 15;12(4):1660-1670. eCollection 2022.
Prostate cancer (PCa) incidence and mortality rate vary among racial and ethnic groups with the highest occurrence in African American (AA) men who have mortality rates twice that of Caucasians (CA). In this study, we focused on differential expression of proteins in AA prostate cancer compared to CA using Protein Pathway Array Analysis (PPAA), in order to identify protein biomarkers associated with PCa racial disparity. Fresh frozen prostate samples (n=90) obtained from radical prostatectomy specimens with PCa, including 25 AA tumor, 21 AA benign, 23 CA tumor, 21 CA benign samples were analyzed. A total of 286 proteins and phosphoproteins were assessed using PPAA. By PPAA analysis, 33 proteins were found to be significantly differentially expressed in tumor tissue (n=48, including both CA and AA) in comparison to benign tissue (n=42). We further compared protein expression levels between AA and CA tumor groups and found that 3 proteins were differentially expressed (P<0.05 and q<5%). Aurora was found to be significantly increased in AA tumors, while Cyclin D1 and HNF-3a proteins were downregulated in AA tumors. Predicted risk score was significantly different between AA and CA ethnic groups using logistic regression analysis. In conclusion, we identified Aurora, Cyclin D1 and HNF-3a proteins as being differentially expressed between AA and CA in PCa tissue. Our study suggests that these proteins might be involved in different pathways that lead to aggressive PCa behavior in AA patients, potentially serving as biomarkers for the PCa racial disparity.
前列腺癌(PCa)的发病率和死亡率在不同种族和族裔群体中存在差异,在非裔美国(AA)男性中发生率最高,其死亡率是白种人(CA)的两倍。在本研究中,我们使用蛋白质通路阵列分析(PPAA),重点研究了与CA相比AA前列腺癌中蛋白质的差异表达,以确定与PCa种族差异相关的蛋白质生物标志物。分析了从前列腺癌根治术标本中获得的新鲜冷冻前列腺样本(n = 90),包括25个AA肿瘤样本、21个AA良性样本、23个CA肿瘤样本和21个CA良性样本。使用PPAA评估了总共286种蛋白质和磷酸化蛋白质。通过PPAA分析,发现与良性组织(n = 42)相比,肿瘤组织(n = 48,包括CA和AA)中有33种蛋白质存在显著差异表达。我们进一步比较了AA和CA肿瘤组之间的蛋白质表达水平,发现有3种蛋白质存在差异表达(P < 0.05且q < 5%)。发现极光激酶在AA肿瘤中显著增加,而细胞周期蛋白D1和肝细胞核因子3α蛋白在AA肿瘤中下调。使用逻辑回归分析发现,AA和CA种族群体之间的预测风险评分存在显著差异。总之,我们确定了极光激酶、细胞周期蛋白D1和肝细胞核因子3α蛋白在PCa组织的AA和CA之间存在差异表达。我们的研究表明,这些蛋白质可能参与了导致AA患者PCa侵袭性的不同途径,有可能作为PCa种族差异的生物标志物。