A cross-sectional study of angiopoietin-1 (Ang-1) in early and advanced prostate cancer

Abstract

5137 Background: Ang-1, a prostate cancer associated angiogenesis growth factor was measured in serum of an age-matched non-cancer cohort and in prostate cancer patients at different stages of tumor progression. Methods: An IRB approved collection of blood specimens in patients with prostate disease was performed in 188 subjects (cancer and non cancer patients). Based on stage of tumor, cancer patients were grouped in four cohorts. Ang-1 levels were measured in serum using commercially available ELISA kits (R & D systems, MN). Results: Hundred and sixty two cancer patients and 26 non-cancer subjects were enrolled. Cancer cohort included Group 1: 51 patients with localized stage cancer prior to radical prostatectomy were enrolled in this group, of which 27 patients had post prostatectomy serum specimens available for serial evaluation of Ang-1 levels; Group 2: patients with early biochemical failure post primary therapy, and prior to initiation of androgen deprivation therapy (ADT) (n=56); Group 3: patients with gross metastasis prior to ADT (n=12); and Group 4: patients with tumor progression during ADT (n=23). Table 1 summarizes PSA and Ang-1 results and comparisons between groups. Conclusions: A significant decrease of serum Ang-1 was observed after prostatectomy in the localized cancer group, even as significant elevation in serum Ang-1 was observed in the pre-prostatectomy stage compared to non-cancer controls. This suggests a role for Ang-1 associated angiogenesis in early stage prostate cancer. Interestingly, lower (than pre-prostatectomy localized stage disease) serum Ang-1 in advanced, grossly metastatic disease may indicate a silencing of the Ang-1-tie2 receptor axis in advanced stage disease possibly secondary to a competitive switching from Ang-1 to Ang-2 with development of metastasis. These findings should be explored further as they have implications in developing therapeutic strategies for targeting angiopoietin nediated angiogenesis in different stages of tumor progression. Serum Ang-1 levels in cancer cohorts and controls Groups (N) Median PSA (ng/ml) (range) P-value Median Ang-1 (ng/ml) (range) P-value Non-cancer (26) vs. pre-treatment Group 1 (51) 5.6 vs. 6.1 (0.8–31.1) vs. (0.08–18.9) 0.31 27.9 vs. 33.5 0.04 Group 1 pre (51) vs. post-treatment (27) 6.1 vs. 0.05 (0.08–18.9) vs. (0–14.6) <0.0001* 30.7 vs. 28.3 0.04* Group 1 post- treatment (27) vs. Group 2 (56) 0.04 vs. 0.79 (0–14.6) vs. (0.01–20.9) 0.0001 28.3 vs. 27.2 0.41 Group 1 pre- treatment (51) vs. Group 3 (12) 6.1 vs. 8.3 (0.08–18.9) vs. (0.01–20.9) 0.52 33.5 vs. 21.5 0.0002 Group 1 pre- treatment (51) vs. Group 4 (23) 6.1 vs. 10.2 (0.08–18.9) vs. (0.7–1352) 0.04 33.5 vs. 23.6 0.002 p-values-Wilcoxon two-sample test; * signed rank test No significant financial relationships to disclose.