title: A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile.
abstract: BACKGROUND
  The incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive <12 months. This poor prognosis is attributable to difficulty of early detection. Here we developed and evaluated a multivariate index composed of plasma free amino acids (PFAAs) for early detection of PC.
  
  
  METHODS
  We conducted a cross-sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography-mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC).
  
  
  RESULTS
  Several amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86-0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84-0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75-0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80-0.93) for all PC patients versus CP patients.
  
  
  CONCLUSIONS
  These findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC.
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Fukutake
authors.affiliation: Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.affiliation: Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Tokai University Oiso Hospital, Kanagawa, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Department of Anesthesia, Gunma Prefectural Cancer Center, Gunma, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Saruki
authors.affiliation: Department of Gastroenterology and Hepatology, Japan Community Healthcare Organization (JCHO), Osaka Hospital, Osaka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yamakado
authors.affiliation: Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ono
authors.affiliation: Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Imaizumi
authors.affiliation: Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Institute for Innovation, Ajinomoto Co., Inc., Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000097:blood; D000596:Amino Acids / Q000097:blood*; D019540:Area Under Curve; D001216:Asparagine / Q000097:blood; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005215:Fasting / Q000097:blood; D005260:Female; D006639:Histidine / Q000097:blood; D006801:Humans; D007532:Isoleucine / Q000097:blood; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000453:epidemiology; D050500:Pancreatitis, Chronic / Q000097:blood; D012372:ROC Curve; D012694:Serine / Q000097:blood; D014364:Tryptophan / Q000097:blood; D055815:Young Adult
chemical_list: D000596:Amino Acids; D007532:Isoleucine; D012694:Serine; D006639:Histidine; D001216:Asparagine; D014364:Tryptophan; D000409:Alanine