title: Clinicopathological characteristics and diagnostic performance of Wisteria floribunda agglutinin positive Mac-2-binding protein as a preoperative serum marker of liver fibrosis in hepatocellular carcinoma.
abstract: BACKGROUND
  Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+)-M2BP) is a novel serum marker of liver fibrosis identified in glycoproteomic biomarker screening studies, and its clinicopathological characteristics have yet to be elucidated sufficiently for clinical utilization.
  
  
  METHODS
  We retrospectively analyzed the clinicopathology data and serum WFA(+)-M2BP levels in 376 hepatocellular carcinoma patients undergoing liver surgery. WFA(+)-M2BP was quantified in frozen serum samples collected at the time of surgery using the FastLec-Hepa method.
  
  
  RESULTS
  Significant independent determinants of serum WFA(+)-M2BP levels included pathological diagnosis of cirrhosis, female gender, hepatitis C virus (HCV) infection, and liver dysfunction characteristics, such as abnormal indocyanine green retention rate at 15 min, platelet counts, albumin levels, alanine aminotransferase levels, and total bilirubin levels. Serum WFA(+)-M2BP levels increased with the pathological fibrosis stage and liver dysfunction severity. HCV infection significantly affected serum WFA(+)-M2BP levels throughout the pathological and functional progression of liver fibrosis, and the effect of gender was significant only in F4 stage patients with severe liver dysfunction. The diagnostic thresholds for cutoff index values for cirrhosis were 1.435 and 4.615 in HCV-negative and HCV-positive patients, respectively. Serum WFA(+)-M2BP levels at the time of operation were a significant predictor of hepatocellular carcinoma recurrence and overall survival in both HCV-negative and HCV-positive patients.
  
  
  CONCLUSIONS
  Serum WFA(+)-M2BP levels reflected both the pathological and functional progression of liver fibrosis comprehensively and continuously. Elevated WFA(+)-M2BP levels were a significant risk factor for tumor recurrence and decreased overall survival after liver surgery independent of HCV infection.
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujiyoshi
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, 305-8568, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, 305-8568, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Transplant Surgery, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yokoo
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamachi
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.affiliation: Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, 272-8516, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Korenaga
authors.affiliation: Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, 272-8516, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, 305-8568, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan. taketomi@med.hokudai.ac.jp.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006498:Hepatectomy; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000601:surgery; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D037121:Plant Lectins; D011379:Prognosis; D034781:Receptors, N-Acetylglucosamine; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D008562:Membrane Glycoproteins; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C114782:TAA90K protein, human; C040129:wisteria lectin
keywords: Biomarker; Cirrhosis; Hepatocellular carcinoma; Liver fibrosis; Wisteria floribunda agglutinin positive Mac-2-binding protein