The Dual Role of ANG-2 in Pancreatic Cancer

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is well-known for its inflammatory nature. Inflammation leads to secretion of Angiopoietin-2 (Ang-2), which works in vascular remodeling. Increased Ang-2 can be detected in endothelial cells and in the circulation in various cancers. High circulating Ang-2 is a marker for shorter survival in PDAC. Different from other tumours, in addition to the endothelial expression, PDAC cells themselves express Ang-2. The correlation between tumour cell Ang-2 expression and survival is still unknown, and the aim of this study was to look into this relationship. Method: Ang-2 immunohistochemistry (IHC) staining was done on 158 PDAC patient samples and staining intensity scored by two examiners (range: negative (0) to strongly positive (3)). We measured circulating Ang-2 levels in sera of 196 patients with ELISA (DuoSet methodology). The results were assessed with respect to clinical data and patient outcomes. Results: Neither circulating Ang-2 nor tumour expression was affected by patient characteristics. Disease specific survival (DSS) was shorter in patients with a negative to weak tumour Ang-2 expression (0.95 years, IQR 1.99), when compared to those with an intermediate to high expression (1.84 years, IQR 2.73, p<0.017). In contrast, higher than median (≥2.72ng/ml) circulating Ang-2 associated with shorter DSS (1.49 years, IQR 2.02) when compared to patients with low circulating Ang-2 (2.17years, IQR 2.49, p=0.002). Conclusion: Ang-2 has a dual role in PDAC with respect to survival. Further studies are needed to find the mechanisms that cause tumour cell Ang-2 expression and its beneficial association with respect to survival.