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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Serum Mac-2 binding protein is a novel biomarker for chronic pancreatitis
Tomohiro Maekawa, Yoshihiro Kamada, Yusuke Ebisutani, Makiko Ueda, Tomoki Hata, Koichi Kawamoto, Shinji Takamatsu, Kayo Mizutani, Mayuka Shimomura, Tomoaki Sobajima, Hironobu Fujii, Kotarosumitomo Nakayama, Kimihiro Nishino, Makoto Yamada, Takashi Kumada, Toshifumi Ito, Hidetoshi Eguchi, Hiroaki Nagano, Eiji Miyoshi
Tomohiro Maekawa, Yoshihiro Kamada, Yusuke Ebisutani, Makiko Ueda, Shinji Takamatsu, Kayo Mizutani, Mayuka Shimomura, Tomoaki Sobajima, Hironobu Fujii, Kotarosumitomo Nakayama, Kimihiro Nishino, Eiji Miyoshi, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
Tomoki Hata, Koichi Kawamoto, Hidetoshi Eguchi, Department of Surgery, Osaka University Graduate School of Medicine Suita, Suita, Osaka 565-0871, Japan
Makoto Yamada, aMs New Otani Clinic, Osaka, Osaka 540-8570, Japan
Takashi Kumada, Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan
Toshifumi Ito, Department of Gastroenterology and Hepatology, Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka 540-8570, Japan
Hiroaki Nagano, Department of Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
Author contributions: Maekawa T and Kamada Y contributed equally to this study; Maekawa T drafted the article; Kamada Y drafted the article, contributed to conception and design; Ebisutani Y, Ueda M, Fujii H, Nakayama K and Nishino K contributed to acquisition and analysis of data; Hata T and Kawamoto K made critical revision of the manuscript; Takamatsu S made interpretation of data; Mizutani K, Shimomura M and Sobajima T contributed to data acquisition and analysis; Yamada M, Kumada T, Ito T, Eguchi H and Nagano H contributed to technical and material support; Miyoshi E contributed to study supervision, critical revision of the manuscript.
Supported by Grants-in-Aid for Scientific Research (B), No. 15H04810 from the Japan Society for the Promotion of Science, Japanese Society of Laboratory Medicine Fund for the Promotion of Scientific Research, Foundation for Total Health Promotion; and supported as a research program from the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan.
Institutional review board statement: This study was reviewed and approved by the ethics committee of Osaka University Hospital (No. 260).
Informed consent statement: Written informed consent was obtained from all subjects at the time of enrollment or blood sampling.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Eiji Miyoshi, MD, PhD, Professor, Chairman, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7, Yamada-oka, Suita, Osaka 565-0871, Japan. emiyoshi@sahs.med.oska-u.ac.jp
Telephone: +81-6-68792590 Fax: +81-6-68792590
Received: January 31, 2016
Peer-review started: January 31, 2016
First decision: March 7, 2016
Revised: March 8, 2016
Accepted: March 18, 2016
Article in press: March 18, 2016
Published online: May 7, 2016
AIM: To determine the efficacy of Mac-2 binding protein (Mac-2bp) for diagnosis of chronic pancreatitis.
METHODS: Fifty-nine healthy volunteers (HV), 162 patients with chronic pancreatitis (CP), and 94 patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer (including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay (carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic (ROC) analyses.
RESULTS: Serum Mac-2bp levels were significantly increased in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp.
CONCLUSION: Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population.
Core tip: Serum Mac-2 binding protein (Mac-2bp) levels were significantly increased in chronic pancreatitis patients compared to healthy volunteers and pancreatic ductal adenocarcinoma patients. Therefore, measurement of serum Mac-2bp is a novel method for diagnosing chronic pancreatitis.
