title: Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination.
abstract: This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n= 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n= 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p< 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994,p< 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01,p= 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. itoi@tokyo-med.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Itoi
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan. msugi@sfc.keio.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. junko.umeda@gmail.com.
authors.forename: Junko
authors.initials: J
authors.lastname: Umeda
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. a-sofuni@amy.hi-ho.ne.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sofuni
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. tsuchiya623@mac.com.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. g.shujiro@gmail.com.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. onakasuicyatta@yahoo.co.jp.
authors.forename: Reina
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. tonozuka1978@gmail.com.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tonozuka
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. honjo3244@yahoo.co.jp.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Honjo
authors.affiliation: Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. moriyasu@tokyo-med.ac.jp.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Moriyasu
authors.affiliation: Third Department of Surgery, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. kasuya-k@jcom.home.ne.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kasuya
authors.affiliation: Third Department of Surgery, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan. naga@tokyo-med.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nagakawa
authors.affiliation: Fourth Department of Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji,Tokyo 193-0998, Japan. abey3666@gmail.com.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Fourth Department of Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji,Tokyo 193-0998, Japan. kiminoriman526@yahoo.co.jp.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Takano
authors.affiliation: Fourth Department of Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji,Tokyo 193-0998, Japan. skawachi@tokyo-med.ac.jp.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawachi
authors.affiliation: Fourth Department of Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji,Tokyo 193-0998, Japan. shimazu2401@yahoo.co.jp.
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan. soga@sfc.keio.ac.jp.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan. mt@sfc.keio.ac.jp.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Fourth Department of Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji,Tokyo 193-0998, Japan. be7@xui.biglobe.ne.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001661:Biliary Tract Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: biliary tract cancers; capillary electrophoresis mass spectrometry; metabolomics; pancreatic cancer