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. 2010 Jul 12;2(3):1453-91.
doi: 10.3390/cancers2031453.

YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

Nicolai A Schultz  1 , Julia S Johansen
Affiliations

YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

Nicolai A Schultz et al. Cancers (Basel). .

Abstract

YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet sufficient data to support determination of plasma YKL-40 outside research projects as a biomarker for screening of gastrointestinal cancer and determination of treatment response and poor prognosis before or during treatment and follow-up. Plasma YKL-40 is also elevated in patients with other diseases than cancer, e.g., severe infections, cardiovascular disease, diabetes, chronic obstructive lung disease, asthma, liver fibrosis and rheumatoid arthritis. Co-morbidity should therefore always be considered in patients with cancer, since other sources than cancer cells can increase plasma YKL-40 levels. Future focused translational research projects combining basic and clinical research are needed in a joint effort to answer questions of the complex function and regulation of YKL-40 and the question if plasma YKL-40 is a clinical useful biomarker in patients with cancer.

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Figures

Figure 1
Figure 1
YKL-40 protein expression determined by immunohistochemical analysis in cultures of human embryonic stem cells (A) and in a biopsy of human embryonal carcinoma (D). Membrane staining of the region enclosed by square labelled B in A (B) or strong cytoplasmatic staining are seen in embryonic stem cells in vitro (C) and in embryonal carcinoma cells in vivo (D).
Figure 2
Figure 2
The number of publications each year regarding YKL-40.
Figure 3
Figure 3
YKL-40 protein expression determined by immunohistochemical analysis in biopsies from patients with different types of cancer. (A) Normal breast epithelium with weak YKL-40 staining and strong staning in inflammatory cells; (B) Invasive ductal carcinoma of the breast with strong, diffuse cytoplasmic staining; (C) Colorectal carcinoma with strong, diffuse cytoplasmic staining; (D) Ovarian carcinoma with moderate, cytoplasmic staining; (E) Squamous cell carcinoma of the head and neck with strong, diffuse cytoplasmic staining; (F) Squamous cell carcinoma of the cervix with strong, diffuse cytoplasmic staining; (G) Melanoma with strong, diffuse cytoplasmic staining; (H) Hepatocellular carcinoma with low cytoplasmic staining (large arrows) and a bile duct with dot-like staining (in Golgi) of normal epithelial cells (small arrows); and (I) Pancreatic carcinoma with strong, diffuse cytoplasmic staining (large arrows) and low staining in normal epithelial cells (small arrows).
Figure 4
Figure 4
The percentage of patients with elevated plasma YKL-40 is calculated as the number of patients in the different studies with plasma YKL-40 higher than the age-adjusted 95th percentile of plasma YKL-40 in healthy subjects.
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