title: Specific increase in serum core-fucosylated haptoglobin in patients with chronic pancreatitis.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignancies, and its diagnosis in early stages is the most important prognostic factor. Chronic pancreatitis (CP), a common background of PDAC occurrence, is morphologically defined as progressive pancreatic fibrosis and inflammation accompanied by pancreatic exocrine cell atrophy. We recently found that inflammation and fibrosis are independent characteristic histological changes in noncancerous lesions in PDAC patients despite the absence of a past history of clinical CP. Subclinical CP is an important background for PDAC occurrence. Therefore, there is an urgent need to develop a noninvasive and reliable biomarker for CP diagnosis.
  
  
  METHODS
  Fifty-nine healthy volunteers (HV), 159 patients with CP, and 83 patients with PDAC were enrolled in this study. We measured serum total fucosylated haptoglobin (Fuc-Hpt) and core-Fuc-Hpt levels using lectin-antibody enzyme-linked immunosorbent assay kits that we developed. In these kits, total Fuc-Hpt and core-Fuc-Hpt were measured using Aleuria aurantia lectin and Pholiota squarrosa lectin, respectively.
  
  
  RESULTS
  Serum Fuc-Hpt levels were significantly increased in CP patients compared to HV (P < 0.0001) and were further increased in PDAC patients (P < 0.0001). Interestingly, serum core-Fuc-Hpt levels were significantly higher in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Multivariate analyses demonstrated that total serum core-Fuc-Hpt was an independent determinant for CP diagnosis, but Fuc-Hpt was not.
  
  
  CONCLUSIONS
  A dramatic change in oligosaccharides was observed in serum haptoglobin between CP and PDAC. Serum core-Fuc-Hpt may be a novel and useful biomarker for CP diagnosis.
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takamatsu
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Shimomura
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sobajima
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Kotarosumitomo
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Nishino
authors.affiliation: aMs New Otani Clinic, Osaka, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamada
authors.affiliation: J-Oil Mills Incorporation, Yokohama, Kanagawa, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Gastroenterology and Hepatology, Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. Electronic address: emiyoshi@sahs.med.oska-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D005260:Female; D015870:Gene Expression; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins
keywords: Chronic pancreatitis (CP); Fucosylated haptoglobin; Fucosylation; Glycoproteins; Lectin-antibody ELISA; Pancreatic ductal adenocarcinoma (PDAC)