Makiko Ueda1, Yoshihiro Kamada1, Shinji Takamatsu1, Mayuka Shimomura1, Tomohiro Maekawa1, Tomoaki Sobajima1, Hironobu Fujii1, Kotarosumitomo Nakayama1, Kimihiro Nishino1, Makoto Yamada2, Yuka Kobayashi3, Takashi Kumada4, Toshifumi Ito5, Hidetoshi Eguchi6, Hiroaki Nagano7, Eiji Miyoshi8. 1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. 2. aMs New Otani Clinic, Osaka, Osaka, Japan. 3. J-Oil Mills Incorporation, Yokohama, Kanagawa, Japan. 4. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan. 5. Department of Gastroenterology and Hepatology, Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan. 6. Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 7. Department of Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. 8. 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.
Abstract
BACKGROUND/ OBJECTIVES: 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.
BACKGROUND/ OBJECTIVES: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 PDACpatients 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 PDACpatients (P < 0.0001). Interestingly, serum core-Fuc-Hpt levels were significantly higher in CP patients compared to HV (P < 0.0001) and PDACpatients (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: Bobby G Ng; Jill A Rosenfeld; Lisa Emrick; Mahim Jain; Lindsay C Burrage; Brendan Lee; William J Craigen; David R Bearden; Brett H Graham; Hudson H Freeze Journal: Am J Hum Genet Date: 2018-11-29 Impact factor: 11.025
Authors: Bobby G Ng; Gege Xu; Nandini Chandy; Joan Steyermark; Deepali N Shinde; Kelly Radtke; Kimiyo Raymond; Carlito B Lebrilla; Ali AlAsmari; Sharon F Suchy; Zöe Powis; Eissa Ali Faqeih; Susan A Berry; David F Kronn; Hudson H Freeze Journal: Am J Hum Genet Date: 2018-01-04 Impact factor: 11.025
Authors: Zobeida Cruz-Monserrate; Kristyn Gumpper; Valentina Pita; Phil A Hart; Christopher Forsmark; David C Whitcomb; Dhiraj Yadav; Richard T Waldron; Stephen Pandol; Hanno Steen; Vincent Anani; Natasha Kanwar; Santhi Swaroop Vege; Savi Appana; Liang Li; Jose Serrano; Jo Ann S Rinaudo; Mark Topazian; Darwin L Conwell Journal: Pancreatology Date: 2021-01-22 Impact factor: 3.996
Authors: Evelina Ferrantelli; Karima Farhat; Agnes L Hipgrave Ederveen; Karli R Reiding; Robert H J Beelen; Frans J van Ittersum; Manfred Wuhrer; Viktoria Dotz Journal: Sci Rep Date: 2018-01-17 Impact factor: 4.379