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

Pancreatology. 2016 Nov-Dec;16(6):1044-1050. doi: 10.1016/j.pan.2016.09.003. Epub 2016 Sep 7.

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.

Keywords: Glycosylation; Mac-2 binding protein; Pancreatic ductal adenocarcinoma; Wisteria floribunda agglutinin.

MeSH terms

  • Antigens, Neoplasm / blood*
  • Biomarkers, Tumor / blood
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Movement
  • DNA, Neoplasm / genetics
  • Fibrosis
  • HEK293 Cells
  • Humans
  • Membrane Glycoproteins / blood*
  • Microarray Analysis
  • Neoplasm Invasiveness / pathology
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / pathology
  • Pancreatitis, Chronic / blood
  • Pancreatitis, Chronic / diagnosis
  • Plant Lectins*
  • Receptors, N-Acetylglucosamine*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Membrane Glycoproteins
  • Plant Lectins
  • Receptors, N-Acetylglucosamine
  • TAA90K protein, human
  • wisteria lectin