Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
Prostate. 2011 May 15;71(7):755-65. doi: 10.1002/pros.21292. Epub 2010 Oct 28.
The peroxiredoxins (PRDXs) are emerging as regulators of antioxidant defense, apoptosis, and therapy resistance in cancer. Because their significance in prostate cancer (PCa) is unclear, we investigated their expression and clinical associations in PCa.
Transcript expression of PRDX1-6 in PCa was evaluated in cancer gene microarray datasets, whereas protein expression was evaluated by immunoblotting in prostate cell lines, and by immunohistochemistry (IHC) in prostate tissue microarrays (TMAs) containing tumor (n = 80) and control (n = 17) tissues. PRDX3 was also analyzed in TMAs containing PCa tissues from African-American and Caucasian patients (n = 150 per group). PRDX expression was correlated with patients' clinicopathologic characteristics.
Analysis of PRDX expression in cancer microarray datasets revealed consistent upregulation (tumor vs. normal) of PRDX3 and 4. All PRDXs exhibited elevated protein expression in PCa cell lines, compared with non-tumor cells. IHC revealed significant overexpression of PRDX3 and 4 in PCa, associated with age, increased prostate specific antigen (PSA), tumor stage, or Gleason score. High PRDX3 staining was associated with early age and elevated Gleason score at time of radical prostatectomy in African-American but not in Caucasian patients with PCa. PSA recurrence free survival in patients with low PRDX3 tumor expression was significantly longer in Caucasians compared to African-Americans, but no difference was detected for high expression.
PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. Their role in PCa development, and their potential as biological determinants of PCa health disparities and novel therapeutic targets, deserve further investigation.
过氧化物酶（PRDXs）作为抗氧化防御、细胞凋亡和癌症耐药性的调节剂而崭露头角。由于它们在前列腺癌（PCa）中的意义尚不清楚，我们研究了它们在 PCa 中的表达及其与临床的关联。
在癌症基因微阵列数据集中评估了 PRDX1-6 在 PCa 中的转录表达，通过免疫印迹法在前列腺细胞系中评估了蛋白表达，并通过免疫组织化学（IHC）在包含肿瘤（n=80）和对照（n=17）组织的前列腺组织微阵列（TMA）中评估了蛋白表达。还在包含来自非裔美国人和高加索患者的 PCa 组织的 TMA 中分析了 PRDX3（每组 n=150）。分析了 PRDX 表达与患者临床病理特征的相关性。
对癌症微阵列数据集中的 PRDX 表达进行分析显示，PRDX3 和 4 的表达一致上调（肿瘤与正常）。与非肿瘤细胞相比，所有 PRDX 在 PCa 细胞系中均表现出蛋白表达升高。IHC 显示 PRDX3 和 4 在 PCa 中显著过表达，与年龄、前列腺特异性抗原（PSA）升高、肿瘤分期或 Gleason 评分有关。在接受根治性前列腺切除术的非裔美国患者中，PRDX3 染色高与年龄较小和 Gleason 评分升高有关，但在高加索患者中则没有差异。PRDX3 肿瘤低表达患者的 PSA 无复发生存期在高加索患者中明显长于非裔美国人，但高表达时则没有差异。
PRDXs 在前列腺肿瘤中表现出差异表达，PRDX3 和 4 一致上调。它们在 PCa 发展中的作用及其作为 PCa 健康差异和新型治疗靶点的生物学决定因素的潜力值得进一步研究。
