Osteopontin splice variant as a potential marker for metastatic disease in pancreatic adenocarcinoma

Abstract

Osteopontin (OPN) is a phosphoprotein that activates pathways that induce cancer cell survival and metastasis. Our aim was to examine the expression pattern of OPN splice variants a, b, and c in fine-needle aspirates and to determine their correlation with stage-adjusted pancreatic ductal adenocarcinoma (PDA) survival. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed in patients with solid pancreatic masses. The tissue was collected and analyzed for the expression of OPN isoforms by reverse transcription-polymerase chain reaction. Survival curves of stages and overexpression of OPN splice variants (a, b, c) were estimated according to the Kaplan-Meier and the log-rank test. EUS-FNA was performed in 46 patients with solid pancreatic lesions (40 PDA and 6 chronic pancreatitis). OPNa was highly expressed in 39/40 (98%), OPNb in 24/40 (60%), while OPNc was present in 10/40 (25%) of PDA samples. The median survival was lower in patients whose fine-needle aspiration (FNA) samples expressed OPNb than those without (406 days vs 749 days, P = 0.049). There was no significant difference in survival in patients with OPNc. Cox proportional hazard model demonstrated that OPNb expression had a trend toward decrease overall survival (P = 0.06), with these patients having a hazard of death three times higher than those without. OPNc was found to significantly correlate with metastatic disease (P = 0.009) in PDA patients. Our data show for the first time that in FNA samples, there is a strong association between OPNc and presence of metastasis in PDA, and OPNb and poor survival.