Serum YKL-40, A New Prognostic Biomarker in Cancer Patients?

Johansen, Julia S.; Jensen, Benny Vittrup; Roslind, Anne; Nielsen, Dorte; Price, Paul A.

doi:10.1158/1055-9965.epi-05-0011

Cited by 280 publications

(317 citation statements)

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“…1 Both tumor cells and tumor-associated macrophages produce YKL-40. 2 Plasma YKL-40 is high in patients with gastrointestinal, [3][4][5] breast, 6 lung, 7 prostate 8 and other cancer, [9][10][11] and is also associated with tumour burden and prognosis after a cancer diagnosis. 5,[12][13][14][15][16] Furthermore, high plasma YKL-40 predicts high risk of gastrointestinal cancer in the general population.…”

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confidence: 99%

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Kjærgaard

Nordestgaard

Johansen

et al. 2015

Intl Journal of Cancer

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Plasma YKL-40 is high in patients with cancer and in individuals who later develop cancer. Whether YKL-40 is only a marker or indeed a cause of cancer is presently unknown. We tested the hypothesis that observationally and genetically, high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population. Plasma levels of YKL-40 were measured in 21,643 and CHI3L1 rs4950928 was genotyped in 94,568 individuals. From 1943 through 2011, 2,291 individuals developed gastrointestinal cancer, 913 developed lung cancer, 2,863 women developed breast cancer, 1,557 men developed prostate cancer and 5,146 individuals developed other cancer. Follow-up was 100% complete. Multifactorially and CRP adjusted hazard ratio (HR) for gastrointestinal cancer was 1.82 (95%CI, 1.16-2.86) for 96-100% versus 0-33% YKL-40 percentile category. Corresponding HR were 1.71 (0.95-3.07) for lung cancer, but insignificant for breast cancer, prostate cancer and other cancers. CHI3L1 rs4950928 genotype was associated with plasmaYKL-40 levels, but not with risk of any cancer category. For gastrointestinal cancer, a doubling in YKL-40 was associated with a multifactorially and CRP adjusted observational HR of 1.14(1.05-1.23) for gastrointestinal cancer, but a corresponding genetic odds ratio of 1.06(0.94-1.18). For lung cancer, corresponding risk estimates were 1.11(1.00-1.22) observationally and 1.01(0.84-1.20) genetically. For other cancer categories, observational and genetic findings were insignificant. This study shows that high plasma YKL-40 levels were associated with high risk of gastrointestinal and likely of lung cancer, but genetic high levels were not.Inflammation plays an important role in cancer development and/or progression. 1 Both tumor cells and tumor-associated macrophages produce YKL-40. 2 Plasma YKL-40 is high in patients with gastrointestinal, 3-5 breast, 6 lung, 7 prostate 8 and other cancer, 9-11 and is also associated with tumour burden and prognosis after a cancer diagnosis. 5,[12][13][14][15][16] Furthermore, high plasma YKL-40 predicts high risk of gastrointestinal cancer in the general population. 17 Whether YKL-40 is only a marker of inflammation and cancer or plays a causal role in the development of cancer is presently unknown.A single nucleotide polymorphism in the proximal promoter of chitinase-3-like-1 (same as YKL-40; CHI3L1), rs4950928, accounts for 9.4% of the variance of plasma YKL-40. 18 MYC/MAX transcriptional factors bind better to the major than to the minor allele of rs4950928 in the gene promoter, 19 thereby presumably increasing CHI3L1 transcription and elevating plasma YKL-40 levels in carriers of the major versus minor allele. [20][21][22] We tested the hypothesis that observationally and genetically high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population...

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confidence: 99%

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Kjærgaard

Nordestgaard

Johansen

et al. 2015

Intl Journal of Cancer

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“…29,30 High YKL-40 levels in serum have been reported to be closely associated with shorter survival in various types of solid tumors, including glioblastoma, 31 suggesting that YKL-40 could be useful as a prognosticator for cancer survival. 32 Interestingly, high YKL-40 levels are also predictive of second-line chemoresistance in ovarian cancer. 33 In VEGF siRNA glioma, CHI3L1 and the related CHI3L2 were both amongst the highest up-regulated genes, suggesting a critical role of chitinase-like proteins in regulating response of tumor cells to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

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Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti‐angiogenic agents used increasingly in the clinic. However, to be efficient, anti‐VEGF agents need to be associated with classic chemotherapy. Exploring gene regulation in tumor cells during anti‐angiogenesis might help to comprehend the molecular basis of response to treatment. To generate a defined anti‐angiogenic condition in vivo, we transfected human glioma cells with short‐interfering RNAs against VEGF‐A and implanted them on the chick chorio‐allantoic membrane. Gene regulation in avascular tumors was studied using human Affymetrix™ GeneChips. Potentially important genes were further studied in glioma patients. Despite strong VEGF inhibition, we observed recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL‐40, a putative prognosticator for various diseases, including cancer, were strongly up‐regulated in avascular glioma. In glioblastoma patients, these genes showed coregulation and their expression differed significantly from low‐grade glioma. Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004) were significantly correlated with poor survival. Cox regression analysis further confirmed that PI3 and CHI3L1 levels are survival markers independent from patient age and sex. Elafin‐positive tumor cells were only found in glioblastoma, where they were clustered around necrotic areas. PI3/elafin is strongly induced by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results indicate that anti‐angiogenesis in experimental glioma drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and new therapeutic targets. © 2007 Wiley‐Liss, Inc.

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“…Un nouveau chapitre 4 , allant cette fois jusqu'au niveau de la « vraie » séquence au lieu de se limiter à un catalogue des Snips et de leurs associations en haplotypes. Concrètement, cela signifie que les chercheurs qui à l'avenir découvriront une association entre une région donnée du génome et la vulnérabilité à une maladie pourront directement accéder à un catalogue détaillé des variants existants dans cette zone et pourront alors tester chacun de ces variants dans des études fonctionnelles.…”

Section: Resultsunclassified

“…Certains éléments du remodelage bronchique seraient peu ou pas sensibles aux traitements instaurés, notamment à base de corticostéroïdes et ils pourraient contribuer à la survenue d'une obstruction bronchique irréversible, source de handicap fonctionnel parfois sévère [7]. Ainsi, l'identification, au niveau ou à distance du poumon, de biomarqueurs du remodelage bronchique en mesure de et les cancers pulmonaires à petites cellules [2][3][4]. Le plus souvent, YKL-40 était localisée au niveau de sites qui étaient le siège d'une fibrogenèse active et de remaniements de la matrice extracellulaire.…”

Section: Chitine Et Chitinasesunclassified

Du mollusque à l’homme

Pretolani

2008

Med Sci (Paris)

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Serum YKL-40, A New Prognostic Biomarker in Cancer Patients?

Abstract: YKL-40, a member of the ''mammalian chitinase -like

Cited by 280 publications

References 98 publications

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Du mollusque à l’homme

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