Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

PLoS One. 2013 Jun 26;8(6):e67059. doi: 10.1371/journal.pone.0067059. Print 2013.

Abstract

Purpose: We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.

Patients and methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • CA-19-9 Antigen / blood*
  • Chitinase-3-Like Protein 1 / blood*
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / surgery
  • Pancreatitis / blood
  • Prognosis
  • Risk
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • Chitinase-3-Like Protein 1
  • Interleukin-6

Grants and funding

The study was supported by grants from “The Research Council at Herlev Hospital” and the ”Joint Proof-of-Concept Fund, the Ministry of Science, Technology and Innovation, Denmark”. Quidel provided the study with some of the YKL-40 ELISA kits. The study sponsors had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. The authors had full access to all the data in the study and had the final responsibility for the decision to submit the manuscript for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.