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The Prognostic Value of Plasma YKL-40 in Patients With Chemotherapy-Resistant Ovarian Cancer Treated With Bevacizumab
  1. Mogens K. Boisen, MD, PhD,
  2. Christine V. Madsen, MD, PhD,
  3. Christian Dehlendorff, MSc, PhD,
  4. Anders Jakobsen, MD, DMSc,
  5. Julia S. Johansen, MD, DMSc and
  6. Karina D. Steffensen, MD, PhD
  1. * Department of Oncology, University of Copenhagen Herlev Hospital, Herlev;
  2. Department of Oncology, Vejle Hospital, Vejle;
  3. Danish Cancer Society, Danish Cancer Society Research Center, Copenhagen;
  4. § Department of Medicine, University of Copenhagen Herlev Hospital, Herlev; and
  5. Faculty of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  1. Address correspondence and reprint requests to Mogens K. Boisen, MD, PhD, Department of Oncology, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail: Mogens.Karsboel.Boisen{at}


Objective YKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patients with ovarian cancer treated with bevacizumab.

Methods One hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during treatment. Both raw YKL-40 concentrations and age-corrected percentiles of normal YKL-40 level were used. Associations between plasma YKL-40 level and progression-free survival (PFS) and overall survival were tested using univariate and multivariate Cox proportional hazards models.

Results Baseline plasma YKL-40 levels were higher in patients with poor performance status, less differentiated tumors, residual disease after primary surgery, higher than the median serum CA-125 level, and higher than the median serum vascular endothelial growth factor level. Age-corrected percentile of normal plasma YKL-40 greater than the lowest quartile (Q1, 85th percentile) was associated with shorter PFS in univariate (hazard ratio, 1.83; 95% confidence interval, 1.15–2.89; P = 0.010) and multivariate analyses and shorter overall survival in univariate analysis (hazard ratio, 1.96; 95% confidence interval, 1.27–3.03; P = 0.003). Increase in plasma YKL-40 during bevacizumab treatment, with correction for baseline plasma YKL-40, was a predictor of shorter PFS. Using normal versus elevated plasma YKL-40 as a cutoff did not provide the same discriminative value.

Conclusions Low plasma YKL-40 at baseline and during treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab.

  • CHI3L1
  • YKL-40
  • Bevacizumab
  • Plasma
  • Biomarker
  • Ovarian cancer
  • Predictive
  • Prognostic

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  • The authors declare no conflicts of interest.