Pretherapeutic circulating endostatin levels in patients with gastric cancer

Abstract

10095 Background: Endostatin is an antiangiogenic fragment of collagen XVIII and is generated by tumor-derived proteases. The functional activity of circulating endostatin is currently unknown. This is the first report on serum endostatin in gastric cancer. Methods: A total of 111 patients with gastric cancer (52 metastatic patients and 59 patients undergoing gastrectomy without distant metastasis) were included in the study. Forty eight of 52 (92%) metastatic patients received systemic chemotherapy. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA and compared with the levels in 30 healthy controls. Data were analyzed using Student’s t-test and one-way ANOVA to compare means between groups, and using Spearman rank correlation to assess correlations between clinicopathologic factors and serum endostatin and VEGF levels. Survival curves were analyzed and compared using the Kaplan-Meier method and log-rank test. Results: Mean serum endostatin and VEGF levels were higher in gastric cancer patients than in healthy controls (endostatin, 69.8 ± 16.3 vs. 52.8 ± 6.0 ng/ml [P <0.001]; VEGF, 55.2 ± 7.5 vs. 31.9 ± 2.5 ng/ml [P <0.001]). Endostatin and VEGF levels were significantly higher in sera from metastatic patients than in sera from patients without distant metastasis (endostatin, 79.5 ± 17.9 vs. 61.3 ± 8.2 ng/ml [P <0.001]; VEGF, 57.4 ± 7.3 vs. 53.2 ± 7.2 ng/ml [P = 0.003]). There was a significant association between endostatin levels and the presence of distant metastases (r= 0.674; P <0.001). A correlation was also observed between serum endostatin and VEGF levels (r= 0.718; P <0.001). There was no significant difference in serum endostatin according to depth of tumor invasion, Lauren’s classification, differentiation, or regional lymph node status. A serum endostatin level higher than the median (78.14 ng/ml) was associated with a poor prognosis in metastatic gastric cancer (last follow- up at 42 months, median survival time 9 vs. 20 months [P=0.02]). Conclusions: In gastric cancer patients, serum endostatin levels are elevated and correlate with circulating VEGF levels as well as the presence of distant metastases. The endostatin level at diagnosis of metastatic gastric cancer may be useful for predicting survival time. No significant financial relationships to disclose.