Serum YKL-40 Independently Predicts Outcome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

Zhu, Cheng-Bao; Wang, Can; Chen, Lili; Ma, Guoliang; Zhang, Shi-Cai; Liang, Shuli; Tian, Jianjun Paul; Gai, Zhongtao

doi:10.1371/journal.pone.0044648

Cited by 15 publications

(13 citation statements)

References 22 publications

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“…Rath et al ( 62 ) suggested that YKL-40 was a powerful fibrosis marker with high diagnostic accuracy, particularly in HCV-associated liver disease. Moreover, our results revealed that the greatest significant increase was detected in HCC patients, which was consistent with Zhu et al ( 63 ). Pelloski et al ( 64 ) suggested that serum levels of YKL-40 serve as a diagnostic and prognostic cancer biomarker.…”

Section: Discussionsupporting

confidence: 93%

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma

Mm¹,

Sa²,

El‐Ahwany³

et al. 2015

Electron physician

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IntroductionHepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-β1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process. YKL-40 is a glycoprotein member of ECM and plays a role in cancer cell proliferation. The purpose of this study was to determine the serum biomarkers of EMT and its impact on the fibrogenic process and tumorigenesis in HCV-genotype 4 patients.MethodsIn this case-control study that was conducted in 2013–2014, 97 HCV-infected patients were subjected to clinical examination, laboratory investigations, and liver biopsy. According to the histopathologic examination, they were classified to F0 (14 cases), F1 (17 cases), F2 (15 cases), F3 (18 cases), F4 (22 cases), and HCC (11 cases). Fifteen age- and gender-matched subjects were included as normal controls. Serum levels of TGF-β1, BMP-7, CTGF, YKL-40 were assessed, and the TGF-β1/BMP-7 ratios were calculated. The data were analyzed by plotting the receiver operating characteristic curve (ROC), Pearson product-moment correlation coefficient, and Spearman’s rank correlation coefficient (Spearman’s rho).ResultsSerum levels of TGF-β1, BMP-7, CTGF, and YKL-40 were significantly increased in all patient groups compared to controls (p < 0.001). LC exhibited the highest CTGF level and YKL-40 was highest in HCC. The TGF-β1/ BMP-7 ratios reflected the progression of EMT from CHC to LC, however, there was no significant difference between LC and HCC. TGF-β1/ BMP-7 ratio is considered to reflect positive correlation with CTGF in LC group (r = 0.629; p < 0.03) and YKL-40 in HCC group (r = 0.504; p < 0.04).ConclusionIncreased TGF-β1/BMP-7 ratio and CTGF levels reflect the rate of EMT and provide information about fibrogenic activity. Also, this ratio, in association with YKL-40, can be used to predict malignant transformation in HCV-genotype 4 Egyptian patients.

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Section: Discussionsupporting

confidence: 93%

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma

Mm¹,

Sa²,

El‐Ahwany³

et al. 2015

Electron physician

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“…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. 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.…”

mentioning

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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“…Elevated levels of serum YKL-40 were reported to be associated with several types of cancer, such as ovarian, esophageal, breast, lung, liver and kidney cancer (11)(12)(13)(14)(15)(16). Furthermore, high expression of YKL-40 is associated with tumor grade, poor differentiation and shorter overall survival times, and may be a potential biomarker (5,11,13).…”

Section: Discussionmentioning

confidence: 99%

Potential suppressive effects of theophylline on human rectal cancer SW480 cells inï¿½vitro by inhibiting YKL-40 expression

Peng

Zeng

et al. 2018

Oncol Lett

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Abstract. Chitinase-3-like-1 protein (YKL-40), a member of the mammalian chitinase-like glycoproteins, serves a key role in the pathogenesis of rectal cancer. The present study examined the antitumor effect of theophylline, a pan-chitinase inhibitor, in rectal cancer in vitro and investigated the mechanism by which it acted. SW480 cell lines were treated with varying theophylline concentrations (10 -2 , 10 -3, 10 -4 and 10 -5 mol/l). An MTT assay was used to observe cell proliferation and identify the optimal theophylline concentration. Western blotting was used to analyze YKL-40 expression. The cell cycle distribution of SW480 cell lines treated with theophylline was measured by flow cytometry. The angiopoietin-2 expression level was measured by ELISA. The expression levels of YKL-40 were evidently decreased in theophylline-treated SW480 cell lines. The proliferation ofSW480 cells was inhibited following theophylline treatment, which was associated with G 1 phase cell cycle arrest and a decrease in the expression of angiopoietin-2. The mechanism of theophylline action may involve the downregulation of YKL-40 expression, arrest of the cell cycle at G 1 phase and inhibition of angiopoietin-2 expression. These results provide a rationale for the potential use of anti-YKL-40 and anti-angiogenic strategies in treating rectal cancer.

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Serum YKL-40 Independently Predicts Outcome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

Cited by 15 publications

References 22 publications

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma

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

Potential suppressive effects of theophylline on human rectal cancer SW480 cells inï¿½vitro by inhibiting YKL-40 expression

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