title: Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine.
abstract: BACKGROUND
  Better pancreatic cyst fluid biomarkers are needed.
  
  
  OBJECTIVE
  To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Tertiary-care referral center.
  
  
  METHODS
  Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts.
  
  
  METHODS
  Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed.
  
  
  METHODS
  Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve).
  
  
  RESULTS
  Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts.
  
  
  CONCLUSIONS
  Small sample sizes.
  
  
  CONCLUSIONS
  Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.
authors.affiliation: Department of Medicine, Stanford University, Stanford, California, USA. wgpark@stanford.edu
authors.forename: Walter G
authors.initials: WG
authors.lastname: Park
authors.forename: Manhong
authors.initials: M
authors.lastname: Wu
authors.forename: Raffick
authors.initials: R
authors.lastname: Bowen
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: William L
authors.initials: WL
authors.lastname: Fitch
authors.forename: Reetesh K
authors.initials: RK
authors.lastname: Pai
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wodziak
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Visser
authors.forename: George A
authors.initials: GA
authors.lastname: Poultsides
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Norton
authors.forename: Subhas
authors.initials: S
authors.lastname: Banerjee
authors.forename: Ann M
authors.initials: AM
authors.lastname: Chen
authors.forename: Shai
authors.initials: S
authors.lastname: Friedland
authors.forename: Brennan A
authors.initials: BA
authors.lastname: Scott
authors.forename: Pankaj Jay
authors.initials: PJ
authors.lastname: Pasricha
authors.forename: Anson W
authors.initials: AW
authors.lastname: Lowe
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000378:metabolism; D015331:Cohort Studies; D020420:Cyst Fluid / Q000378:metabolism*; D003536:Cystadenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D018282:Cystadenocarcinoma, Mucinous / Q000175:diagnosis / Q000378:metabolism; D003537:Cystadenoma / Q000175:diagnosis / Q000378:metabolism*; D018291:Cystadenoma, Mucinous / Q000175:diagnosis / Q000378:metabolism; D018293:Cystadenoma, Serous / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D010181:Pancreatic Cyst / Q000175:diagnosis / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D010192:Pancreatic Pseudocyst / Q000175:diagnosis / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D007737:Kynurenine; D005947:Glucose
keywords: CEA; CI; IPMN; IQR; LC/MS; MCN; MS; ROC; SCA; carcinoembryonic antigen; confidence interval; interquartile range; intraductal papillary mucinous neoplasm; liquid chromatography with mass spectrometry; mass spectrometry; mucinous cystic neoplasm; receiver operating characteristic; serous cystadenoma