Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 16; no. 6; pp. 1044 - 1050
• Main Authors: Waragai, Yuichi, Suzuki, Rei, Takagi, Tadayuki, Sugimoto, Mitsuru, Asama, Hiroyuki, Watanabe, Ko, Kikuchi, Hitomi, Hikichi, Takuto, Masamune, Atsushi, Kang, Ya'an, Fleming, Jason B, Ohira, Hiromasa
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01-11-2016; Elsevier Limited
• Subjects: Antigens; Antigens, Neoplasm - blood; Biomarkers, Tumor - blood; Calcification; Carcinoma, Pancreatic Ductal - blood; Carcinoma, Pancreatic Ductal - pathology; Cell culture; Cell Movement; DNA, Neoplasm - genetics; Endocrinology & Metabolism; Experiments; Fibrosis; Gastroenterology and Hepatology; Glycosylation; HEK293 Cells; Humans; Immunoassay; Mac-2 binding protein; Medical research; Membrane Glycoproteins - blood; Metastasis; Microarray Analysis; Neoplasm Invasiveness - pathology; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - pathology; Pancreatitis, Chronic - blood; Pancreatitis, Chronic - diagnosis; Plant Lectins; Proteins; Receptors, N-Acetylglucosamine; Wisteria floribunda agglutinin; Mac-2 binding protein; Glycosylation; Wisteria floribunda agglutinin; Pancreatic ductal adenocarcinoma
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1016/j.pan.2016.09.003

Abstract Background Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+ -M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA+ -M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis. Methods In this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA+ -M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA+ -M2BP, we investigated the presence of WFA+ -M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53). The bio-physiological effects of MDA-PATC53 supernatant were evaluated. Finally, the difference in the expression of glycosylation enzymes between MDA-PATC53 and Panc-1 were analyzed by cDNA microarray. Results We found that the serum WFA+ -M2BP level could distinguish the 2 groups. The median serum COI of WFA+ -M2BP was 0.98 and 0.51 in PDAC and CP, respectively. Additionally, WFA+ -M2BP positive PDACs were more frequently associated with metastatic lesions than the WFA+ -M2BP negative PDACs (91.6% vs. 41.7%, P  = 0.009). The MDA-PATC53 cells alone produced WFA+ -M2BP. However, we found that MDA-PATC53 supernatant containing WFA+ -M2BP (1.0 COI) did not alter the biological behavior of cancer cell lines. The results of cDNA microarray revealed that several glycosylation enzymes with pro-oncologic function were highly expressed in MDA-PATC53 compared to Panc-1. Conclusions Serum WFA+ -M2BP can be a useful biomarker for the diagnosis of PDAC and the prediction of disease progression since it potentially reflects altered pro-oncologic glycosylation enzymes.