Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma

Abstract

Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumorderived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 6 16.6 vs. 52.2 6 6.2 ng/mL [p < 0.001]; VEGF, 55.1 6 7.6 vs. 32.1 6 2.4 ng/mL [p < 0.001]; mean 6 SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r 5 0.556, p < 0.001) and VEGF levels (r 5 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p 5 0.017]; median time to progression, 5 vs. 10 months [log-rank, p 5 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome. ' 2006 Wiley-Liss, Inc.

Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma

“…Based on the results, the investigators suggested a significant correlation between collagen XVIII expression in tumor tissue and elevated serum endostatin levels [14]. Previously, we showed that higher levels of serum endostatin are linked with poorer prognosis in metastatic gastric carcinoma [18]. In this study, we examined whether collagen XVIII expression is associated with the serum endostatin level in gastric cancer (data not shown).…”

“…However, the role of collagen XVIII in tumor progression and prognosis of hepatocellular carcinoma remains a controversial [13,20]. Previously, we reported an association of elevated pretreatment serum endostatin levels in metastatic gastric carcinoma with poor survival and rapid tumor progression [18]. To our knowledge, the clinical significance of collagen XVIII expression in gastric cancer has not been investigated.…”

“…Phase II clinical trials using recombinant endostatin for treatment of advanced neuroendocrine tumors showed 80% of stable disease, although no patient displayed partial or complete response, according to the WHO criteria [9]. Elevated serum levels of endostatin are associated with poor outcome in several cancers [10][11][12][13][14][15][16][17][18]. Endogenous serum level of endostatin may reflect counteractions with active angiogenesis in tumor progression.…”

Gastric Cancer and Angiogenesis: Is VEGF a Useful Biomarker to Assess Progression and Remission?

“…Additionally, Woo et al [26] concluded that pretherapeutic serum endostatin (P<0.001) and VEGF (P<0.001) levels were higher in patients with GC. The serum endostatin (P<0.001) and VEGF (P=0.001) levels were significantly higher in patients with metastasis than in patients without distant metastasis.…”

172: Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

“…Despite the acknowledged antiangiogenic functions of endostatin, higher serum endostatin levels are associated with poor differentiation and advanced stage in CRC, gastric cancer and bladder cancer (Li et al, 2012;Szarvas et al, 2012) and with poor prognosis of the patient in bladder cancer, non-small cell lung cancer, gastric cancer and soft tissue sarcoma (Feldman et al, 2001;Suzuki et al, 2002;Woo et al, 2006;Szarvas et al, 2012). The effect of endostatin on endothelial cells depends on the length of exposure (Li et al, 2005), the type of endothelial cells (Schmidt et al, 2004) and the type of growth factor inducing endothelial cell proliferation (Delaney et al, 2006).…”