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

By Ali Siddiqui, Elizabeth Jones, Darren Andrade, Apeksha MD Shah, Thomas E Kowalski, David E Loren, Galina Chipitsyna and Hwyda A Arafat


BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Topics: Department of Internal Medicine, Division of Gastroenterology, Department of Surgery, Thomas Jefferson University; Adenocarcinoma, Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Endosonography, Female, Gene Expression, Genetic Association Studies, Genetic Variation, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Metastasis, Osteopontin, Pancreatic Neoplasms, Proportional Hazards Models, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Tumor Markers, Biological, Adenocarcinoma, Aged, 80 and over, Biopsy, Fine-Needle, Tumor Markers, Biological, Gastroenterology
Publisher: Jefferson Digital Commons
Year: 2014
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