title: Identification of highly sensitive biomarkers that can aid the early detection of pancreatic cancer using GC/MS/MS-based targeted metabolomics.
abstract: BACKGROUND
  To improve prognosis of pancreatic cancer (PC) patients, the discovery of more reliable biomarkers for the early detection is desired.
  
  
  METHODS
  Blood samples were collected by 2 independent groups. The 1st set was included 55 early PC and 58 healthy volunteers (HV), and the 2nd set was included 16 PC and 16HV. The 16 targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry together with their corresponding stable isotopes. In the 1st set, the levels of these metabolites were evaluated, and diagnostic models were constructed via multivariate logistic regression analysis, leading to validation using the 2nd set.
  
  
  RESULTS
  In the 1st set, model X consisting of 4 candidates based on our previous report possessed higher sensitivity (74.1%) than carbohydrate antigen 19-9 (CA19-9). Model Y, consisting of 2 metabolites newly selected from 16 metabolites via stepwise method possessed higher sensitivity (70.4%) than CA19-9. Furthermore, combining model Y with CA19-9 increased its sensitivity (90.7%) and specificity (89.5%). In the 2nd set, combining model Y with CA19-9 displayed high sensitivity (81.3%) and specificity (93.8%). In particular, it displayed very high sensitivity (100%) for resectable PC.
  
  
  CONCLUSIONS
  Quantitative analysis confirmed that metabolomics-based diagnostic methods are useful for detecting PC early.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Fujigaki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Iemoto
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Departments of Hepato-Biliary-Pancreatic Surgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.affiliation: Department of Oral Surgery, Osaka Medical College, Osaka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shimahara
authors.affiliation: Department of Oral Surgery, Osaka Medical College, Osaka, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuchida
authors.affiliation: Department of Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Sata
authors.affiliation: Department of GI Cancer Screening and Surveillance, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ioka
authors.affiliation: Islet Institute, Fukuoka University, Fukuoka, Japan.
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Yasunami
authors.affiliation: Department of Gastrointestinal Surgery, JR Tokyo General Hospital, Tokyo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.affiliation: Department of Radiology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneda
authors.affiliation: Department of Oral Implant, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Oral Surgery, Saitama Cancer Center, Saitama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yagihara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan; Japan Agency for Medical Research and Development (AMED) CREST, Tokyo, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan; Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Hyogo, Japan; AMED-CREST, AMED, Hyogo, Japan. Electronic address: myoshida@med.kobe-u.ac.jp.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Early detection; GC/MS/MS; Metabolomics; Pancreatic cancer