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Serum Angiopoietin-2 as a Clinical Marker for Lung Cancer^*

*From the Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea.

Correspondence to: Kwang Joo Park, MD, PhD, Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon, Gyeonggi-do 443–721, South Korea; e-mail: parkkj{at}ajou.ac.kr

Abstract

Background: Angiopoietins play a critical role in the angiogenesis related to tumor growth in concert with vascular endothelial growth factor (VEGF), and enhanced expression of angiopoietin-2 has been reported in lung cancer tissue.

Methods: Patients with lung cancer (n = 136) and healthy volunteers (n = 40) were enrolled. Serum angiopoietin-2 and VEGF concentrations were measured using enzyme-linked immunosorbent assay.

Results: Patients with lung cancer had higher serum angiopoietin-2 (2,046.3 ± 1,171.3 pg/mL vs 1,269.8 ± 494.1 pg/mL, p < 0.001) and VEGF (542.9 ± 445.8 pg/mL vs 364.7 ± 185.9 pg/mL, p < 0.05) [mean ± SD] levels than the control group. Serum angiopoietin-2 and VEGF levels correlated with each other in patients with lung cancer (Spearman r = 0.30, p < 0.001), specifically in non-small cell lung cancer (NSCLC) [n = 110; r = 0.34; p < 0.001] but not in small cell lung cancer (n = 26). With stage progression in NSCLC, serum angiopoietin-2 levels increased, and patients with distant metastasis had higher levels than those without metastasis (p < 0.005). By contrast, serum VEGF level did not increase with stage progression, and only had a trend toward elevation in distant metastasis (p = 0.05). In NSCLC, the low angiopoietin-2 group (< 1,605.5 pg/mL) had a better overall survival compared to the high angiopoietin-2 group ( 1,605.5 pg/mL; p < 0.05), although this survival benefit was not maintained after controlling for stage in a multivariate analysis. The angiopoietin-2 levels were higher in NSCLC patients with postoperative recurrence than in those without.

Conclusions: Our study suggests that serum angiopoietin-2 is a useful clinical marker for detecting NSCLC with distant metastasis and is of potential prognostic value.

Key Words: angiogenesis • angiopoietin-2 • lung cancer • metastasis • non-small cell lung cancer • survival • vascular endothelial growth factor