Angiopoietin-like protein 2 as a novel biomarker for diagnosis and prognosis in esophageal cancer.

Abstract

73 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and overexpression of ANGPTL2 is known to act as a causative mediator of chronic inflammatory carcinogenesis. Recently, expression in tumor cells which are associated with tumor progression has been recognized in lung, breast, colon and gastric cancer. However, to our knowledge, functional and clinical significance of ANGPTL2 expression has not been investigated in esophageal cancer (EC). Aim: We investigated the functional roles of ANGPTL2 in vitro assay and evaluated the clinical significance of ANGPTL2 expression in both primary tumor and matched serum in patients with EC. Materials and Methods: First, in vitro assays were performed for functional analysis of ANGPTL2 using small interfering RNA (siRNA). Next, ANGPTL2 expression in EC tissues was evaluated by immunohistochemically (IHC) in 71 EC patients. Finally, we investigated serum ANGPLT2 levels from EC patients (n=71) and healthy controls (n=35) by ELISA. Results: Knockdown of ANGPTL2 expression decreased proliferative, invasive and migrated capacity in EC cell lines. ANGPTL2 expression in EC tissues was significantly elevated in EC patients with high T stage, squamous cell carcinoma, and high TNM stage. Kaplan–Meier analysis showed that patients with high expression of ANGPTL2 had significantly poorer overall (p<0.01) and disease-free survival (p<0.01) than those with low expression, respectively. Furthermore, multivariate analysis revealed that high ANGPTL2 expression in EC tissues was an independent predictive marker for poor prognosis (HR: 2.30, p=0.04). On the other hands, serum ANGPTL2 levels in EC patients was significantly elevated compared to healthy controls (p<0.001), and it can discriminate EC patients from healthy controls with high accuracy (AUC=0.913). However, no significant association between serum ANGPTL2 levels and clinicopathological findings were recognized in EC patients. Conclusions: We have demonstrated several novel evidences for biological and clinical significance of ANGPTL2 in EC. This study indicates ANGPTL2 had the potential to be useful as a biomarker in EC.