Elevated serum level of YKL‐40 is an independent prognostic factor for poor survival in patients with metastatic melanoma

Johansen, Julia S.; Gehl, Julie; Geertsen, Poul F.; Fode, Kirsten; Maase, Hans von der

doi:10.1002/cncr.21678

Cited by 113 publications

(101 citation statements)

References 41 publications

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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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“…Blood levels of CHi3L1 are negligible under normal physiologic conditions, however, elevated blood levels of CHi3L1 have been found in patients with chronic inflammatory conditions [25] and a wide variety of cancers including colorectal [22,26] , breast [27] , prostate [28] , lung [29,30] , thyroid [31] , endometrial [32] pancreatic [33] hepatocellular [34] , ovarian [35] , gastric cancer [36] , and malignant melanoma [37] . Additionally, for the majority of these malignancies, a correlation has been demonstrated between blood levels of CHi3L1 and a poor prognosis [26,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] . Also, increased expression of CHi3L1 in CRC has been shown to be strongly associated with increased microvascular density [22] .…”

Section: Introductionmentioning

confidence: 99%

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

Kumara

Gaita

Miyagaki

et al. 2016

WJGO

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AIM:To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC). METHODS: CRC patients in an Institutional ReviewBoard approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in RESULTS:PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/ mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), 136.9; n = 62), 287.4; n = 22), 137.4; n = 20, P = 0.001).No significant difference in plasma levels were noted on POD27-41.CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.

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“…Serum YKL-40 has been shown to be a helpful diagnostic and prognostic indicator in various types of cancers, which include colorectal, 19 breast, 20 lung, 21 head and neck, 22 prostate, 23 ovarian cancer, 24 and malignant melanoma. 25 Depending on the tumor type, the effect of serum YKL-40 on survival rates may be substantial (hazard ratio range, 1.3-4.1). 26 Most recently, a Danish cohort study showed that elevated YKL-40 level predicts the increased risk of gastrointestinal cancer and decreased survival after cancer diagnosis in general population.…”

Section: Discussionmentioning

confidence: 99%

Utility of Serum YKL-40 as a Tumor-Specific Marker of Hepatobiliary Malignancies

et al. 2010

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Background/Aims: Serum YKL-40 has been linked to several human cancers. We investigated the potential role of serum YKL-40 as a marker of hepatobiliary malignancies. Methods: Archived serum samples of patients undergoing liver transplantation evaluation at the Mayo Clinic Rochester were used to measure YKL-40 levels. Patients were divided into three groups: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and end-stage liver disease (ESLD) without malignancies. The Model for ESLD (MELD) score was used to quantify the severity of liver disease. Results: The median serum YKL-40 level was highest in the ESLD group at 296 ng/mL, compared to 259 ng/mL in the HCC group and 80 ng/mL in the CCA group (p＜0.01). There was a significant correlation between the MELD score and serum YKL-40 level (r=0.50, p＜0.01). In a multivariate analysis, there was no significant difference in serum YKL-40 level between ESLD and HCC. CCA was associated with lower YKL-40 levels, a finding that was attributable to a lower prevalence of cirrhosis. Conclusions: The serum YKL-40 level has little utility as a cross-sectional screening tool for hepatobiliary malignancies, namely HCC and CCA. The role of YKL-40 as a surveillance marker in the follow-up of individual patients remains to be determined. (Gut Liver 2010;4:537-542)

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Elevated serum level of YKL‐40 is an independent prognostic factor for poor survival in patients with metastatic melanoma

Cited by 113 publications

References 41 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

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

Utility of Serum YKL-40 as a Tumor-Specific Marker of Hepatobiliary Malignancies

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