title: Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer.
abstract: We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.
  
  
  
  In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.
  
  
  
  Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).
  
  
  
  Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark ; Department of Oncology Copenhagen University Hospital at Herlev, Denmark ; Department of Surgical Gastroenterology, Copenhagen University Hospital at Herlev, Herlev, Denmark ; Department of Medicine, Copenhagen University Hospital at Herlev, Herlev, Denmark.
authors.forename: Nicolai A
authors.initials: NA
authors.lastname: Schultz
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.forename: Nathalia
authors.initials: N
authors.lastname: Giese
authors.forename: Benny V
authors.initials: BV
authors.lastname: Jensen
authors.forename: Ole
authors.initials: O
authors.lastname: Larsen
authors.forename: Jon K
authors.initials: JK
authors.lastname: Bjerregaard
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.forename: Dan
authors.initials: D
authors.lastname: Calatayud
authors.forename: Svend E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: Mette K
authors.initials: MK
authors.lastname: Yilmaz
authors.forename: Niels H
authors.initials: NH
authors.lastname: Holländer
authors.forename: Morten
authors.initials: M
authors.lastname: Wøjdemann
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.forename: Kaspar R
authors.initials: KR
authors.lastname: Nielsen
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood*; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000601:surgery; D010195:Pancreatitis / Q000097:blood; D011379:Prognosis; D012306:Risk; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D000071451:Chitinase-3-Like Protein 1; D015850:Interleukin-6