Abstract 2715: Peroxiredoxin 3: A potential biological determinant of prostate cancer health disparities

Abstract

Abstract Prostate Cancer (PCa) is the most frequently diagnosed male cancer and presents the greatest racial disparity of any cancer in the U.S., with high incidence and mortality among African American (AA) men. Eliminating these disparities requires a multi-prong approach that includes, in addition to aggressive social and public health interventions, a better understanding of the biology of prostate tumors from different ethnic groups, and the development of effective treatments for castration-resistant prostate cancer (CRPC). Our interest is to define the contribution of antioxidant and stress proteins induced by environmental factors to tumor aggressiveness and health disparities in PCa. We analyzed the expression of the peroxiredoxin (PRDX) protein family in prostate cell lines and prostate tissue microarrays (TMA), and observed a dramatic upregulation of PRDX3 in androgen responsive metastatic cell lines, particularly the AA-derived cell line MDA-PCa-2b. There was also a significant correlation between high PRDX3 tissue expression and PCa (when compared to normal tissues), advanced tumor stage, and elevated PSA (P<0.05). These observations prompted an analysis of PRDX3 protein expression in ethnicity PCa TMAs containing 150 cases from AA PCa patients and 150 cases from Caucasian (CC) PCa patients, plus normal prostate tissues. Although we did not observe significant differences in the percent of PRDX3-positive immunostained prostate tumor tissues when comparing AA vs CC tissues, high PRDX3 expression correlated with early age at diagnosis (P<0.01) and elevated Gleason score (P<0.05) in the AA group but not in the CC group (P=0.459 and P=0.3394, respectively). We also examined the association between PRDX3 prostate tumor tissue expression and PSA recurrence free survival in AA and CC patients for which disease progression data was available. PSA recurrence free survival in patients with low PRDX3 tumor expression was longer in the CC group than in the AA group (P<0.05, log rank test), suggesting a correlation with a more favorable prognosis for the CC patients. However, no statistically significant difference in PSA recurrence free survival was detected in patients with high PRDX3 expression, when both groups were compared (P=0.159). These results could be interpreted as that high PRDX3 expression in prostate tumors is associated with a less favorable prognosis regardless of ethnicity, whereas low PRDX3 expression is associated with a less favorable prognosis in AA patients compared to CC patients. The contribution of PRDX3 to these differences is unclear, but taken together the data suggest that the presence of PRDX3 (low or high) in prostate tumors from AA patients could be associated with a more aggressive disease phenotype. These results warrant further investigation of the significance of PRDX3 expression in prostate tumors, and exploiting PRDX3 as a novel therapeutic target for CRPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2715.