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      International Journal of COPD (submit here)

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      The YKL-40 protein is a potential biomarker for COPD: a meta-analysis and systematic review

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          Abstract

          Background

          Many studies have found that YKL-40 may play an important pathogenic role in COPD. However, the results of these studies were inconsistent. Therefore, we performed a systematic review and meta-analysis to investigate the role of YKL-40 in COPD.

          Methods

          We performed a systematic literature search in many database and commercial internet search engines to identify studies involving the role of YKL-40 in patients with COPD. The standardized mean difference (SMD) and Fisher’s Z-value with its 95% confidence interval (CI) were used to investigate the effect sizes.

          Results

          A total of 15 eligible articles including 16 case–control/cohort groups were included in the meta-analysis. The results indicated that the serum YKL-40 levels in patients with COPD were significantly higher than those in healthy controls (SMD =1.58, 95% CI =0.68–2.49, P=0.001), and it was correlated with lung function (pooled r=−0.32; Z=−0.33; P<0.001). The results of subgroup analysis found that the serum YKL-40 levels were statistically different between the exacerbation group and the stable group in patients with COPD (SMD =1.55, 95% CI =0.81–2.30, P<0.001). Moreover, the results indicated that the sputum YKL-40 levels in patients with COPD were also significantly higher than those in healthy controls (SMD =0.70, 95% CI =0.10–1.30, P=0.022).

          Conclusion

          The current study suggests that YKL-40 may be implicated in bronchial inflammation and remodeling in COPD and may be considered as a useful biomarker for COPD diagnosis and monitoring.

          Most cited references32

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          Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation.

          Chitin is a surface component of parasites and insects, and chitinases are induced in lower life forms during infections with these agents. Although chitin itself does not exist in humans, chitinases are present in the human genome. We show here that acidic mammalian chitinase (AMCase) is induced via a T helper-2 (Th2)-specific, interleukin-13 (IL-13)-mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma. AMCase neutralization ameliorated Th2 inflammation and airway hyperresponsiveness, in part by inhibiting IL-13 pathway activation and chemokine induction. AMCase may thus be an important mediator of IL-13-induced responses in Th2-dominated disorders such as asthma.
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            YKL-40, a secreted glycoprotein, promotes tumor angiogenesis

            Tumor angiogenesis is of paramount importance in solid tumor development. Elevated serum levels of YKL-40, a secreted heparin-binding glycoprotein have been associated with a worse prognosis from a variety of advanced human cancers. Yet the role of YKL-40 activity in these cancers is still missing. Here, we have shown that ectopic expression of YKL-40 in MDA-MB-231 breast cancer cells and HCT-116 colon cancer cells led to larger tumor formation with an extensive angiogenic phenotype than did control cancer cells in mice. Affinity purified recombinant YKL-40 protein promoted vascular endothelial cell angiogenesis in vitro, the effects similar to the activities observed using MDA-MB-231 and HCT-116 cell conditioned medium after transfection with YKL-40. Further, YKL-40 was found to induce the coordination of membrane-bound receptor syndecan-1 and integrin αvβ3 and activate an intracellular signaling cascade including focal adhesion kinase and MAP kinase Erk1/2 in endothelial cells. Also, blockade of YKL-40 using siRNA gene knockdown suppressed tumor angiogenesis in vitro and in vivo. Immunohistochemical analysis of human breast cancer revealed a correlation between YKL-40 expression and blood vessel density. These findings provide novel insights into angiogenic activities and molecular mechanisms of YKL-40 in cancer development.
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              The global economic burden of asthma and chronic obstructive pulmonary disease.

              Non-communicable diseases are now the number one cause of disabilities and loss of life expectancy. Among them, chronic respiratory conditions constitute a major class. The burden of chronic respiratory diseases is generally increasing across the globe, and asthma and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality and morbidity. However, the direct and indirect costs of these conditions vary across jurisdictions. This article reports on recent estimates of the costs of asthma and COPD, with a focus on comparing disease burden across different regions. Overall, there is tremendous variation in per capita annual costs of asthma and COPD. However, the methodology of the cost-of-illness studies is also vastly different, making it difficult to associate differences in reported costs to differences in the true burden of asthma and COPD. Suggestions are provided towards improving the validity and comparability of future studies.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                30 January 2018
                : 13
                : 409-418
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China
                [2 ]The Center of Gerontology and Geriatrics, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China
                [3 ]Health Management Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China
                [4 ]Lung Cancer Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China
                Author notes
                Correspondence: Panwen Tian; Hong Fan, Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Guo Xue Xiang 37, Chengdu, Sichuan 610041, People’s Republic of China, Tel/fax +86 28 8542 3331, Email 13550351753@ 123456163.com ; fanhongfan@ 123456qq.com
                Article
                copd-13-409
                10.2147/COPD.S152655
                5796800
                29430175
                6c19a8f4-6f01-464f-9c51-d6b4da3ea51a
                © 2018 Tong et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Respiratory medicine
                ykl-40,copd,biomarker,meta-analysis
                Respiratory medicine
                ykl-40, copd, biomarker, meta-analysis

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