Research progress of YKL-40 protein in ocular diseases / 中国医师杂志

YKL-40 protein, also called chitinase 3 like 1 (CHI3L1), is a highly conserved secreted glycoprotein in racial evolution, belonging to the " 18-glycosyl hydrolase" family. A large number of studies have shown that YKL-40 is involved in the pathological process of many diseases. There is little research information about YKL-40 in ocular diseases yet. This article mainly summarizes the research progress of YKL-40 in ocular diseases in the domestic and foreign literatures to provide reference for further clinical research.

Role of YKL-40 in the Microenvironment of Glioblastoma / 中国生物化学与分子生物学报

Glioblastoma (GBM) is the most common malignant tumor of the brain and central nervous system. The complex tumor microenvironment of glioblastoma is considered as the main challenge for clinical treatment of glioblastoma, also the main reason for the high recurrence rate and low survival rate of glioblastoma patients. YKL-40, a secreted protein, is associated with poor prognosis in many types of solid tumors. The expression of YKL-40 in serum and tumor tissues is significantly increased in high-grade gliomas, especially in glioblastoma patients. While this feature is not found in low-grade gliomas, indicating that the expression of YKL-40 is closely related to glioma grade and malignant development. Targeted therapy using YKL-40 antibody together with ionizing radiation has also been shown to synergistically inhibit tumor angiogenesis and malignant progression in glioblastoma patients. Based on the important role of YKL-40 in regulating the tumor microenvironment, this paper summarizes the research progress of YKL-40 in malignant tumors, and discusses the related role of YKL-40 in the occurrence and development of glioblastoma and its clinical application prospect.

Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury / 北京大学学报(医学版)

OBJECTIVE@#To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection.@*METHODS@#Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens.@*RESULTS@#A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05).@*CONCLUSION@#The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

Association between YKL-40 and liver fibrosis / 临床肝胆病杂志

YKL-40 is an emerging inflammatory marker with the highest expression level in the liver. This article summarizes the research advances in YKL-40 as a serological marker for liver fibrosis. The analysis shows that YKL-40 can effectively evaluate the severity of liver fibrosis and thus holds promise for clinical application. Due to limited diagnostic efficiency of a single index, the combination of YKL-40 diagnostic model and other serological markers will become a research hotspot in the future.

YKL-40 Levels in Rheumatoid Arthritis and Their Correlation with Disease Activity: A Meta-analysis

OBJECTIVE: To examine the relationship of serum/plasma YKL-40 levels with rheumatoid arthritis (RA) and their correlation with RA activity and rheumatoid factor (RF) level. METHODS: We performed a meta-analysis comparing the serum/plasma YKL-40 levels between patients with RA and controls and examined the correlation coefficients of the circulating YKL-40 level with the RF level and RA activity based on the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. RESULTS: Nine studies (707 patients with RA and 1,041 controls) were included in the meta-analysis. The YKL-40 levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD]=1.071, 95% confidence interval [CI]=0.726~1.417, p100) populations. Meta-analysis of correlation coefficients showed a significant positive correlation between the YKL-40 levels and DAS28, ESR, CRP level, and RF level (DAS28: correlation coefficient=0.381, 95% CI=0.044~0.640, p=0.028; RF level: correlation coefficient=0.341, 95% CI=0.176~0.487, p<0.001). CONCLUSION: The circulating YKL-40 levels are high in patients with RA and positively correlate with RA activity and RF level.

Elevated plasma YKL-40 level is found in the dogs with cancer and is related to poor prognosis

YKL-40, a secreted glycoprotein, may serve as an autoantigen, which mediates multiple inflammatory diseases and cancers. A high YKL-40 serum level is correlated with metastasis and poor survival in a variety of human cancers. However, the role of YKL-40 in dogs is still under evaluation. Herein, we examined the associations between plasma YKL-40 level and YKL-40 autoantibody (YAA) titers with malignancy and prognosis in canine cancer. Plasma levels of YKL-40 in healthy dogs (n = 20) and in dogs (n = 82) with cancer were evaluated using enzyme-linked immunosorbent assay. Our results indicated that plasma YKL-40 levels were significantly higher (p 180 pg/mL) than in the low YKL-40 group (< 180 pg/mL). The results imply that plasma YKL-40 levels might have the potential to be developed as a marker of malignancy progression and prognosis in canine cancers.

Assessment of potential biomarkers of atherosclerosis in Indian patients with type 2 diabetes mellitus

Background & objectives: Various biological markers of subclinical atherosclerosis have been proposed to predict cardiovascular events in patients with diabetes mellitus (DM). However, there are only a few clinical studies assessing the role of invasive biomarkers [CD-36, peroxisome proliferator-activated receptor gamma (PPAR-?) and YKL-40] in Indian patients with type 2 DM (T2DM). Hence, the present study was conducted to assess protein levels and gene expression of CD-36, PPAR-? and YKL-40 in patients with T2DM and compare that with hypertensive and healthy controls. Methods: All the participants were subjected to medical history, anthropometric measurements and biochemical and biomarker (ELISA and real-time polymerase chain reaction) estimations. The study groups consisted of patients with T2DM (>5 yr) with hypertension (n=55), patients with T2DM (<2 yr) without hypertension (n=28), hypertensive controls (n=31) and healthy controls (n=30). Results: Gene expressions of YKL-40 and CD36 were significantly higher in patients with T2DM (>5 yr) with hypertension compared to healthy controls (P=0.006). In addition, a significant increase in serum levels of sCD36, PPAR-? and YKL-40 was observed in patients with T2DM (>5 yr) with hypertension compared to healthy controls (P<0.05). Serum levels as well as gene expression of CD36 showed significant correlation with serum levels as well as gene expression of PPAR-? (?=0.45 and ?=0.51; P<0.001), respectively. Interpretation & conclusions: CD36 and YKL-40 may be potential inflammatory biomarkers for early onset of atherosclerosis in patients with T2DM.

Association of articular cartilage YKL-40 levels with osteoarthritis / 实用医学杂志

Objective To determine the association of articular cartilage (AC) levels of YKL-40 with osteoarthritis (OA) at different stages of symptomatic severity in patients with knee OA.Methods 42 patients with knee OA were recruited into this study.The radiographic disease severity of OA was assessed by the Kellgren-Lawrence (K-L) grading system.11 patients with non knee OA were selected as normal control group.AC levels of YKL -40 were explored by immunohistochemical method.Symptomatic severity was determined using Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from OA patients.Results YKL-40 levels in AC were positively related to WOMAC pain,function scores and total scores.WOMAC stiffness scores did not correlated with YKL-40 concentrations in AC.The correlation between AC YKL-40 levels and WOMAC scores was further analyzed by multinomial logistic regression.Multiple regression analysis showed that the correlation between AC YKL-40 levels and WOMAC scores was still significant after adjusting for other confounding factors.AC YKL-40 levels were significantly correlated with K-L grading in patients with knee OA.Conclusions YKL-40 in AC can be used as a potential biomarker for assessing the symptomatic severity of OA.

The correlation between YKL-40,sCD40L,AFP and coronary heart disease / 国际检验医学杂志

Objective To study the chitin enzyme protein(YKL-40),sCD40L,AFP and the correlation of hypertension with cor-onary heart disease(CHD).Methods 75 cases of elderly patients with CHD were selected as observation group,and then were di-vided into hypertension group and non hypertension group according to the blood pressure.103 cases of healthy elderly were select-ed as control group.ELISA method was used to detect YKL-40 and sCD40L,and AFP was detected by chemiluminescence immuno-assay.Results Clinical data comparison revealed that the relative risk of CHD with hypertension group and non hypertension of hy-perlipidemia,drinking,smoking,diabetes mellitus,were 1.56,1.33,1.23,1.15 times,data show that relative risk of CHD with hy-pertension were much greater than CHD without hyperlipidemia.The concentration of YKL-40 in CHD with hypertension(92.66± 12.04)ng/mL was significant higher than that in CHD without hypertension (57.08 ± 10.07 )ng/mL,and the concentration of sCD40L in CHD with hypertension (186.59 ± 69.63 )ng/mL was significant higher than that in CHD without hypertension (128.14±48.37)ng/mL(P 0.05).Conclusion The levels of YKL-40,CD40L and AFP in the peripheral blood of elderly patients with CHD were significantly increased.And the concentration of sCD40L and YKL-40 was positively correlated with hy-pertension,which can be used to assess the stability and prognosis of CHD.

The expressions and related discussion of YKL-40 and IL-1β in the cartilage of knee osteoarthritis / 重庆医学

Objective To study the expressions of YKL-40 and IL-1β in the cartilage of knee osteoarthritis(KOA),and analysis the possible relationship between YKL-40,IL-1β in KOA.Methods Thirty-eight patients diagnosed with KOA were selected in this hospital as observation group.Then select 30 articular cartilage cases in the same period due to knee injury knee joint examina tion or treatment of knee joint fracture surgery patients,referred to as the control group.According to KOA radiation and arthroscopic grading standards,the observation group was divided into 16 cases of mild group,10 cases of moderate group,11 cases of severe groups.Compare the expression levels of all patients including YKL-40,interleukin-1β (IL-1β),IL 6,tumor necrosis factor-α (TNF-α),while recording Mankin score and cell mortality.Results Expression of YKL 40,IL-1β,IL-6,TNFα,Mankin scores and rate of cell death about observation group were significantly higher than control group,the indicators above in mild,moderate,severe group showed a trend of rising(all P＜0.05).And the expression levels of YKL-40 and IL-1β were significantly positive correlation (r=0.738,P=0.000).In addition, The expression levels of YKL-40 had relation with IL 6 (r=0.819,P=0.000),TNF-α (r=0.871,P=0.000) and Mankin score (r=0.832,P 0.000),cells mortality deposit (r=0.832,P=0.000).Conclusion Expression levels of YKL-40 and IL-1β were significantly increased in cartilage of knee osteoarthritis patients,and there showed a significant positive correlation between YKL-40 and IL-1β.

Influence on the proliferation of breast cancer with silencing YKL-40 by siRNA interference / 中国现代普通外科进展

Objective:To explore the relationship between YKL-40 and the proliferation of breast cancer and its mechanism.Methods:The expression of YKL-40 in breast cancer MCF-7 cells was detected by immunofluorescence assay.Fluorescence microscope was used to observe the conversion efficiency,and Real-time PCR was used to screen the most effective YKL-40 siRNA.Expression levels of PI3K,P-PI3K,AKT,P-AKT of the PI3K/AKT pathway associated proteins was test by Western blot.At the same time,MTT and flow cytometry were validated by YKL-40 siRNA treatment of human breast cancer MCF-7 ceils,the differences of 24h,48h and 72h groups of cell proliferation ability and cell cycle.Result:MCF-7 cell express YKL-40 protein,mainly located in the cytoplasm.Real-time PCR show that siRNA01,siRNA02,siRNA03 compared with NC group YKL-40 gene silencing effect is remarkable.Among of them the strongest silencing effect is siRNA02 (P＜0.01),Western blot show the experimental group than the control group,Total PI3K and AKT remain unchanged while P-PI3K,P-AKT expression decreased (P＜0.05).In the experimental group,the number of G1 cells in the control group was increased (P＜0.01),while the S phase cells decreased (P＜0.01).MTT results showed that the experimental group compared with the control group,the proliferation ability is decreased(P＜0.01).Conclusions This study suggests that YKL-40 can be used as the upstream regulatory factor of PI3K/AKT signaling pathway and affect the process of cell cycle in breast cancer,and then regulate the proliferation of breast cancer,YKL-40 may be a crucial target for the treatment of breast cancer.

The role of YKL-40 in inflammatory response and its related signaling pathways / 医学研究生学报

YKL-40, a newly found inflammatory marker, is belonged to the mammals′chitinase family.It showed that YKL-40 can participate in a variety of inflammatory diseases such as airway inflammatory diseases, cardiovascular and neurological inflamma-tory diseases, and arthritis etc.It could be used to diagnose and evaluate these inflammatory diseases.Since its specific receptor has not been identified, the exact biological role of YKL-40 in inflammatory response still remains unclear.This article reviews the function of YKL-40 in inflammatory response and its related signaling pathways.

The association between serum YKL-40 levels, mean platelet volume, and c-reactive protein in patients with cellulitis.

Background: Lower limb cellulitis is an infectious disease that has serious complications unless it is treated. Objectives: In this pilot study, we evaluated whether levels of YKL-40, an acute-phase reactant, and mean platelet volume (MPV), which occurs secondary to infl ammation in cellulitis, increase compared to healthy subjects. We also aimed to investigate the association between YKL-40 and MPV in the prognosis of the patients. Material and Methods: A total of 55 patients with cellulitis (23 men and 32 women) and a similar age group of 46 healthy individuals (22 men and 24 women) were included in the study. Cellulitis was diagnosed according to guideline. Serum YKL-40 levels, MPV, C-reactive protein (CRP), and other biochemical values of both groups were compared. Results: YKL-40 levels (52.2 ± 34.5 ng/mL vs 34.6 ± 18.0 ng/mL, P = 0.004), MPV (7.7 ± 1.0 fL vs 6.9 ± 0.7 fL, P < 0.001), and CRP (9.5 ± 8.2 mg/dL vs 0.7 ± 0.6 mg/dL, P < 0.001) were signifi cantly higher in the patients with cellulitis than the control. The mean recovery time (RT) of the patients was 22.6 ± 6.9 days. We found that YKL-40 (odds ratio [OR] 0.1, confi dence interval [Cl] 0.028–0.191, P = 0.009) and MPV (OR 2.4, Cl 0.254-4.578, P = 0.029) have an independent association with RT. Conclusion: YKL-40 and MPV values were correlated with higher CRP in the cellulitis group than in controls. According to these results, increased YKL-40 and MPV levels might be a prognostic factor for cellulitis in patients.

Clinical significance of increased vascular endothelial growth factor, transforming growth factor-beta1, and YKL-40 in the serum of children with asthma

PURPOSE: Vascular endothelial growth factor (VEGF), transforming growth factor beta1 (TGF-beta1), and platelet derived growth factor (PDGF) are known to be involved in the pathogenesis of inflammation and remodeling in asthmatic airways. YKL-40, a chitinase-like protein, and clusterin have been reported to be biomarkers for severe asthma. We examined the serum levels of growth factors, YKL-40, and clusterin in children with acute asthma or stable asthma, and investigated their correlation with clinical findings and lung function parameters. METHODS: Forty-one children (> or =6 years of age) with asthma were enrolled, and 2 groups were defined: 23 patients admitted with acute asthma (acute asthma group) and 18 patients with stable asthma (stable asthma group). The serum levels of VEGF, TGF-beta1, PDGF-BB, YKL-40, and clusterin were measured using enzyme-linked immunosorbent assay and assessed in relation to clinical manifestations and spirometric parameters. Fifteen age-matched controls were also studied. RESULTS: The serum levels of VEGF, TGF-beta1, and YKL-40 were significantly elevated in children with acute asthma compared to controls. The serum levels of VEGF and YKL-40 were higher in the stable asthma group than in controls. The serum levels of VEGF, TGF-beta1, and YKL-40 were not different between the acute asthma and stable asthma groups. The serum VEGF levels in the acute asthma group correlated significantly with asthma severity. The serum TGF-beta1 levels in stable asthma group showed a significant inverse correlation with (FEV1) forced expiratory volume in one second and FEF(25%-75%) (forced expiratory flow between 25 and 75 percent of expired vital capacity). Serum YKL-40 had no significant relationship with clinical manifestations and spirometric parameters. CONCLUSION: Our study suggests that increased serum levels of VEGF and YKL-40 might affect asthmatic airways not only during acute exacerbation but also in stable state and that serum TGF-beta1 might be a biomarker for airway obstruction in children with asthma.

The diagnostic value of YKL-40 and CEA in malignant pleural effusion / 重庆医学

Objective To investigate the diagnostic value of YKL‐40 and CEA in malignant pleural effusion .Methods There were 45 cases of benign pleural effusion and 52 patients with malignant pleural effusion in this study from November 2013 to No‐vember 2014 .Enzyme linked immunosorbent assay(ELISA) and electrochemi lumine scence immunoassay(ECLIA) method were carried out to detect the concentration of YKL‐40 and CEA respectively .The differences of the two groups of patients between YKL‐40 and CEA levels were compared ,and the correlation between YKL‐40 and clinical pathology of malignant pleural effusion were analyzed .In addition ,the receiver‐operating characteristic curve(ROC curve) was used to compare the diagnostic value be‐tween YKL‐40 and CEA .Results The average value of YKL‐40 in malignant pleural effusion was (189 .5 ± 147 .0)ng/mL ,and sig‐nificantly higher than in benign pleural effusion group(P0 .05) .The diagnostic sensitivity and specificity of YKL‐40 was 80 .9% and 51 .2% ,which was lower than CEA(83 .1% and 74 .6% )(P<0 .05) .However ,the sensitivity and specificity was 90 .6% and 88 .2% when combined the two biomarkers together .Conclusion YKL‐40 have a certain clinical diagnostic value in malignant pleural effusion ,it indicate to adenocarcinoma or advanced cancer when the level of YKL‐40 rised .Since the sensitivity and specificity is lower than traditional biomarker of CEA ,we should combine with the other tumor markers to improve the diagnostic accuracy .

YKL-40-induced IL-8 expression from bronchial epithelium leads to bronchial smooth muscle proliferation and migration / 中国免疫学杂志

Objective:To investigate YKL-40-mediated inflammation in human bronchial epithelial cells and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs).Methods:YKL-40-induced inflammation was assayed in two human bronchial epithelial cells (BEAS-2B cell line and primary human bronchial epithelial cells ,namely HBECs).In addition,we treated BEAS-2B cells and HBECs with YKL-40,and added the conditioned culture media ( YKL-40-BEAS-2B-CM) and ( YKL-40-HBECs-CM) to BSMCs.The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent and QCM chemotaxis migration assay ,respectively.Results: Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production,but have no effect about RANTES ,Eotaxin and TNF-α.YKL-40-BEAS-2B-CM and YKL-40-HBECs-CM induced IL-8 was found to further stimulate proliferation and migration of BSMCs ,and the effects were inhibited after neutralizing IL-8.Conclusion:Through investigating the interaction of airway epithelium and smooth muscle ,our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium,subsequently contributing to BSMCs proliferation and migration.Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.

Relationship between Aggrecan and YKL-40 in articular cartilage of Sprague-Dawlay rats with osteoarthritis / 重庆医学

Objective To investigate the relationship between aggrecan and YKL-40 in knee articular cartilage of Sprague-Daw-lay(SD) rats with osteoarthritis (OA) .Methods Fifty-six healthy SD rats were randomly divided into 7 groups ,8 cases per group . The one side of knee joint was randomly selected for performing the anterior cruciate ligment transection (ACLT) and establishing the OA model .The rats in one group were randomly killed on the day of operation and at postoperative 0 ,2 ,4 ,8 ,12 ,16 ,20 weeks . The femoral condyle cartilage samples at different time periods in the operated side were collected for conducting safranin O /fast green staining and HE staining .Meanwhile ,the OA pathological grade was made out according to the modified Mankin scale .The expression of aggrecan and YKL-40 in the cartilage with different stages of OA were analyzed by the immunohistochemistry meth-od ,and the status of expression were measured by average optical density (AOD) .The correlation between aggrecan and YKL-40 was analyzed .Results With the aggravation of OA ,the expression of aggrecan was gradually reduced and the expression of YKL-40 was gradually increased .The differences during the early ,middle and late phases of OA had statistical significance (P<0 .05) . The expression of aggrecan was negatively correlated with the expression of YKL-40(P<0 .05) .Conclusion The level of aggrecan is gradually reduced with the aggravation of OA .Aggrecan is negatively correlated with the YKL-40 level ,which may reflect the dedifferentiation degree of joint chondrocyte to some extent .

The correlation of serum YKL-40 level and albuminuria in type 2 diabetes / 中华内分泌代谢杂志

A total of 175 patients with type 2 diabetes mellitus (T2DM) were composed of 69 with normoalbuminuria,60 with microalbuminuria,and 46 with macroalbuminuria.The control group consisted of 64 healthy individuals.Serum YKL-40 levels were determined with ELISA method and related metabolic data were collected.Serum YKL-40 levels were significantly higher in T2DM group than in control group(P＜0.01).Significant correlations of YKL-40 were found with the ratio of microalbuminuria to uric creatinine(r=0.677,P＜0.01),HbA1C (r =0.562,P＜0.01),systolic blood pressure (r =0.372,P =0.001),HOMA-IR (r =0.460,P =0.001),low density lipoprotein-cholesterol (r=0.304,P=0.012),age(r=0.260,P=0.015),blood uric acid (r=0.329,P=0.018),and high density lipoprotein-cholesterol (r=-0.247,P=0.032).YKL-40 may play a role in the occurrence and development of diabetic nephropathy.

Expression and significance of YKL-40 and VEGF in condyloma acuminatum tissues / 第二军医大学学报

Objective To explore the expression of YKL-40 and vascular endothelial cell growth factor (VEGF) in condyloma acuminatum (CA tissues and the related significance. Methods The expressions of YKL-40 and VEGF were analyzed by immunocytochemical staining with streptavidin-peroxidase (SP) in 33 CA tissues and 10 foreskin tissues of normal person. Results The expression intensities of YKL-40 and VEGF varied largely from positive (#) to strongly positive ($) in CA tissues compared with negative ( - ) and positive ( + ) in normal foreskin tissues. The expressions of YKL-40 and VEGF proteins in CA tissues were significantly different from those in the normal human controls(P0. 05). No correlation was found between the expression of YKL-40 and VEGF proteins in CA tissues (r = 0. 27, P

YKL-40: a Potential Biomarker and Therapeutic Target for Breast Cancer Diagnosis and Therapy.

Over the past two decades, emerging data have found that YKL-40, a secreted glycoprotein, is elevated in a broad spectrum of human diseases including cancers, liver injury, asthma, diabetes, inflammatory diseases, and cardiac disorders. In breast cancer, increased serum levels of YKL-40 are correlated with cancer metastasis and short survival, suggesting that serum levels of YKL-40 serve as a cancer biomarker. YKL-40 has the ability to stimulate vascular endothelial cell activation and suppress mammary epithelial cell differentiation, the pathophysiological events associated with tumor angiogenesis and poor differentiation. Neutralization of YKL-40 via an anti-YKL- 40 monoclonal antibody in animal trials demonstrates the ability of YKL-40 blockade to impede tumor angiogenesis and tumor growth, thus holding therapeutic promise for cancer therapy. Apart from these findings, substantial efforts are urgently required to decipher the key molecular mechanisms that mediate cancer metastasis and malignancy, which is expected to significantly offer translational value for breast cancer diagnosis, prognosis and therapy. This review discusses the current status of research on YKL-40’s expression, biophysiological and pathological activities and functional inhibition, which is instrumental for future clinical practice.