Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma.
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.
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Yuichi
Y
Waragai
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan. Electronic address: subaru@fmu.ac.jp.
Rei
R
Suzuki
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Tadayuki
T
Takagi
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Mitsuru
M
Sugimoto
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Hiroyuki
H
Asama
Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan.
Ko
K
Watanabe
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Hitomi
H
Kikuchi
Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan.
Takuto
T
Hikichi
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Atsushi
A
Masamune
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ya'an
Y
Kang
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jason B
JB
Fleming
Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Hiromasa
H
Ohira
D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000473:pathology; D002465:Cell Movement; D004273:DNA, Neoplasm / Q000235:genetics; D005355:Fibrosis; D057809:HEK293 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000097:blood / Q000175:diagnosis; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C114782:TAA90K protein, human; C040129:wisteria lectin
Glycosylation; Mac-2 binding protein; Pancreatic ductal adenocarcinoma; Wisteria floribunda agglutinin