Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population.

PURPOSE Elevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population. PATIENTS AND METHODS A prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%. RESULTS The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%. CONCLUSION In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.

[1]  H. Nielsen,et al.  Diurnal, Weekly, and Long-Time Variation in Serum Concentrations of YKL-40 in Healthy Subjects , 2008, Cancer Epidemiology Biomarkers & Prevention.

[2]  E. Mizoguchi,et al.  Chitinase 3-like-1 enhances bacterial adhesion to colonic epithelial cells through the interaction with bacterial chitin-binding protein , 2008, Laboratory Investigation.

[3]  B. Nordestgaard,et al.  Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. , 2008, Circulation.

[4]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[5]  I. Christensen,et al.  High serum levels of YKL‐40 in patients with squamous cell carcinoma of the head and neck are associated with short survival , 2008, International journal of cancer.

[6]  V. Castronovo,et al.  Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma , 2007, International journal of cancer.

[7]  M. Schroll,et al.  High serum YKL‐40 level in a cohort of octogenarians is associated with increased risk of all‐cause mortality , 2007, Clinical and experimental immunology.

[8]  L. Larsen,et al.  YKL-40 Protein Expression in the Early Developing Human Musculoskeletal System , 2007, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  B. Dickey Exoskeletons and exhalation. , 2007, The New England journal of medicine.

[10]  J. Dziura,et al.  A chitinase-like protein in the lung and circulation of patients with severe asthma. , 2007, The New England journal of medicine.

[11]  D. Speijer,et al.  Evolution of Mammalian Chitinase(-Like) Members of Family 18 Glycosyl Hydrolases , 2007, Genetics.

[12]  Arjan W. Griffioen,et al.  Tumour vascularization: sprouting angiogenesis and beyond , 2007, Cancer and Metastasis Reviews.

[13]  B. Nordestgaard,et al.  Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. , 2007, JAMA.

[14]  S. Bojesen,et al.  Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population , 2007, The Journal of experimental medicine.

[15]  I. Christensen,et al.  Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival , 2007, Clinical Cancer Research.

[16]  Wan-Wan Lin,et al.  A cytokine-mediated link between innate immunity, inflammation, and cancer. , 2007, The Journal of clinical investigation.

[17]  E. Høgdall,et al.  YKL-40 protein expression in normal adult human tissues – an immunohistochemical study , 2007, Journal of Molecular Histology.

[18]  L. Deangelis,et al.  YKL-40 and Matrix Metalloproteinase-9 as Potential Serum Biomarkers for Patients with High-Grade Gliomas , 2006, Clinical Cancer Research.

[19]  Li Zhang,et al.  Prognostic Associations of Activated Mitogen-Activated Protein Kinase and Akt Pathways in Glioblastoma , 2006, Clinical Cancer Research.

[20]  J. Johansen Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. , 2006, Danish medical bulletin.

[21]  I. Christensen,et al.  Serum YKL-40 predicts relapse-free and overall survival in patients with American Joint Committee on Cancer stage I and II melanoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  D. Nielsen,et al.  Serum YKL-40, A New Prognostic Biomarker in Cancer Patients? , 2006, Cancer Epidemiology Biomarkers & Prevention.

[23]  L. Coussens,et al.  Tumor stroma and regulation of cancer development. , 2006, Annual review of pathology.

[24]  L. Coussens,et al.  Paradoxical roles of the immune system during cancer development , 2006, Nature Reviews Cancer.

[25]  P. Kristjansen,et al.  Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. , 2005, Lung cancer.

[26]  A. Mantovani,et al.  Smoldering and polarized inflammation in the initiation and promotion of malignant disease. , 2005, Cancer cell.

[27]  H. Thaler,et al.  Early detection and prognosis of ovarian cancer using serum YKL-40. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  B. Jensen,et al.  High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[29]  S. Bojesen,et al.  Integrin β3 Leu33Pro Homozygosity and Risk of Cancer , 2003 .

[30]  L. Skovgaard,et al.  Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease. , 2003, Journal of hepatology.

[31]  A. J. Millis,et al.  gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. , 2003, Experimental cell research.

[32]  T. Sørensen,et al.  A prospective study of the association between smoking and later alcohol drinking in the general population. , 2003, Addiction.

[33]  L. Coussens,et al.  Inflammation and cancer , 2002, Nature.

[34]  H. Nielsen,et al.  High serum YKL‐40 level after surgery for colorectal carcinoma is related to short survival , 2002, Cancer.

[35]  H. Ling,et al.  The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. , 2002, The Biochemical journal.

[36]  B. Nordestgaard,et al.  Coronary heart disease risk factors ranked by importance for the individual and community. A 21 year follow-up of 12 000 men and women from The Copenhagen City Heart Study. , 2002, European heart journal.

[37]  R. Collins,et al.  Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. , 1999, American journal of epidemiology.

[38]  H. Kleinman,et al.  Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells. , 1999, Experimental cell research.

[39]  H. Nielsen,et al.  YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. , 1998, Proceedings of the Association of American Physicians.

[40]  J. O'dell,et al.  Chondrex: new marker of joint disease. , 1998, Clinical chemistry.

[41]  L. Shackelton,et al.  Identification of a 38-kDa Heparin-binding Glycoprotein (gp38k) in Differentiating Vascular Smooth Muscle Cells as a Member of a Group of Proteins Associated with Tissue Remodeling (*) , 1995, The Journal of Biological Chemistry.

[42]  I. M. Neiman,et al.  [Inflammation and cancer]. , 1974, Patologicheskaia fiziologiia i eksperimental'naia terapiia.