High Serum YKL-40 Levels Research Articles

Estimation of IL-1β, Osteoprotegerin, and YKL-40: A Diagnostic Array for Prediction of Gestational Diabetes Mellitus complicated by Gestational Hypertension

Objectives: Estimation of serum levels of interleukin (IL)-1β, Osteoprotegerin (OPG) and YKL-40 early in pregnancy of normotensive normoglycemic women to find earlypredictors for development of gestational insulin resistance(GIR), hypertension (GHT) and/or diabetes mellitus(GDM).Patients & Methods: The study included 255 pregnantwomen who were evaluated during their 1st antenatal visit(ANV-1) for age, body mass index (BMI), baseline systolic (SBP) and diastolic blood pressure (DBP) and gaveblood samples for estimation of serum levels of insulin andthe studied cytokines. Then, all women underwent 75-Oralglucose tolerance test (OGTT) for diagnosis of GDM andthe homeostasis model assessment of IR (HOMA-IR) scoreat 6th and 24th GW.Results: 32 women developed GIR that progressed toGDM, 38 women developed GHT, 13 developed GIR andGHT and 7 women developed the triad of GIR, GDM andGHT. There are significant differences in serum IL-1β,YKL-40 and OPG levels in women free and with these disorders. Serum levels of IL-1β showed positive, while serum OPG levels showed negative significant correlationswith the incidence of pregnancy-induced disorders, whilehigh serum YKL-40 was positively correlated with the incidence of GIR with GHT or GDM or both. ROC curveand Regression analyses defined combination of high DBPand serum YKL-40 as the significant early predictors fordevelopment of the three disorders, while high HOMA-IRscore, SBP and serum IL-1β as the significant predictorsfor GHT, high BMI, DBP and serum YKL-40 as early predictors for GIR and GHT and high serum YKL-40 and lowserum OPG levels as early predictors for GIR and DM.Conclusion: Estimation of the studied array of cytokines atthe 1st ANV has a high diagnostic value for the upcomingpregnancy-induced disorders single or combination with higher predictive value than the reliance onclinical data.

Circulating YKL-40 in Philadelphia-negative myeloproliferative neoplasms

ABSTRACT Objectives: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by clonal myeloproliferation and a strong inflammatory atmosphere. YKL-40, expressed in granulocytes, macrophages, megakaryocytes and malignant cells, is an acute phase reactant with an important role in tissue remodeling and atherosclerotic inflammation. The aim of this study was to investigate serum YKL-40 levels in MPNs and to assess its clinical correlations. Methods: ELISA test was used to measure serum YKL-40 levels in 111 MPN patients and in 32 healthy controls. Results: Serum YKL-40 levels were higher in ET, post-ET MF, PV, post-PV MF and primary MF patients, when compared to healthy controls (p < 0.001). Higher serum YKL-40 levels were associated with parameters indicative of the increased inflammatory state (higher C-reactive protein, poor performance status, presence of constitutional symptoms and cardiovascular risk factors). Additionally, higher serum YKL-40 levels in MF patients were associated with blast phase disease, lower hemoglobin and higher Dynamic International Prognostic Scoring System score. In the multivariate Cox regression models, higher serum YKL-40 levels in ET and PV patients were independently associated with an increased risk of thrombosis (HR 4.64, p = 0.031) and impaired survival in MF patients (HR 4.31, p = 0.038). Conclusion: These results indicate that higher circulating YKL-40 levels in MPNs might have a pathophysiological role in disease progression and thrombosis development. Assessing circulating YKL-40 could help in identification of ET and PV patients at a high risk of future cardiovascular events and has a good potential for improving prognostication of MF patients.

The serum YKL-40 level is a potential biomarker for OSAHS: a systematic review and meta-analysis.

Several studies have reported that serum YKL-40 level was elevated in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, most of these studies had relatively small sample sizes and the results were inconsistent. Therefore, a meta-analysis was conducted to determine the potential role of serum YKL-40 level in OSAHS. A systematic literature search was performed in several databases to identify eligible studies involving the relationship between serum YKL-40 level and OSAHS. The standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated to determine the effect sizes. Five eligible articles were extracted in this meta-analysis. The pooled results demonstrated that the serum YKL-40 level was significantly higher in OSAHS patients compared with their non-OSAHS controls (SMD 1.03, 95% CI 0.46, 1.59, I2= 87%, P = 0.0004). The subgroup analysis showed that Asian (SMD 1.81, 95% CI 1.41, 2.21, I2= 0%, P< 0.00001) and Caucasian (SMD 0.67, 95% CI 0.39, 0.96, I2= 0%, P< 0.00001) patients with OSAHS had higher serum YKL-40 levels than their non-OSAHS controls. YKL-40 level in serum was increased in OSAHS patients with BMI< 28 (SMD 1.81, 95% CI 1.41, 2.21, I2= 0%, P< 0.00001), as well as in patients with BMI ≥ 28 (SMD 0.57, 95% CI 0.33, 0.81, I2= 0%, P< 0.00001). In addition, OSAHS patients with cardiac complications had a higher serum YKL-40 level compared with those patients without cardiac complications (SMD 0.80, 95% CI 0.32, 1.28, I2= 67%, P = 0.001). This study indicates that OSAHS patients have higher serum YKL-40 level, which may serve as a potential biomarker for OSAHS diagnosis and monitoring.

Serum levels of YKL-40 are increased in patients with psoriasis: a meta-analysis

ABSTRACTBackground: YKL-40, also named chitinase-3-like protein 1, has been confirmed as an inflammatory glycoprotein associated with cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. Growing evidence has demonstrated that serum levels of YKL-40 in psoriatic patients were increased, however the results were appearance contradictory among the current published studies.Methods: Research involved in serum levels of YKL-40 in psoriatic patients and healthy control individuals was searched in PUBMED, EMBASE, and The Cochrane Library databases (up to 31 December 2018). Weight mean difference (WMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q-statistic and quantified using I2, and publication bias was evaluated using a funnel plot and Egger’s linear regression test. Additionally, the subgroup and sensitivity analyses were also performed.Results: In total, 340 articles were obtained. Among these, 11 studies with 528 psoriatic patients and 460 control individuals were included. Our meta-analysis revealed that psoriatic patients had a higher serum YKL-40 levels compared to the control group, with the WMD of 53.6 ng/ml (95% CI: 31.3 to 75.9, P< 0.001). Furthermore, results of meta-regression analysis and subgroup analysis revealed that the disease duration and the value of psoriasis area and severity index (PASI) were related to the observed YKL-40 differences between two groups.Conclusions: Our meta-analysis indicates that psoriatic patients have higher serum YKL-40 levels when compared to healthy control individuals, and the levels are significantly affected by the disease duration and PASI.

Serum YKL-40 predicts long-term outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

Serum YKL-40, a potential inflammatory marker, is greatly increased at the early stage of ST-segment elevation myocardial infarction (STEMI). Here, we hypothesized that YKL-40 levels at admission could predict the long-term outcomes after STEMI.A total of 324 patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI) were consecutively enrolled and followed for 24 months. The baseline clinical and procedural data were recorded, and serum YKL-40 levels at admission were measured using ELISA method. The endpoint of interest was major adverse cardiac event (MACE), including all-cause death, recurrent myocardial infarction, and hospitalization for heart failure.Patients with elevated serum YKL-40 levels (≥126.8 ng/mL) were more likely to be older and smoker and to present with type 2 diabetes, advanced Killip class, multivessel disease and intra-aortic balloon pump, with increased levels of admission glucose, triglyceride, and high-sensitivity C-reactive protein and decreased level of high-density lipoprotein cholesterol. During the follow-up period, the incidence of MACE was notably higher in the high than in the low YKL-40 groups (28.4% vs 11.1%, P < .001). Kaplan-Meier curve showed that elevated YKL-40 levels were associated with reduced MACE-free survivals (log-rank P < .001). In multivariate Cox regression analysis, we found that high serum YKL-40 level was an independent predictor of MACE after controlling for clinical and angiographic variables (hazard ratio: 1.65, 95% confidence interval: 1.14-2.39, P = .008).The results of our study indicate that serum YKL-40 may be used as a biomarker to predict the long-term outcome after PCI in patients with STEMI.

Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody.

We aimed to investigate the clinical value of checking serum chitinase-3-like-1 protein (YKL-40) levels in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) patients. One hundred and five consecutive anti-MDA5+DM patients and 44 healthy controls were enrolled in this study. Baseline and follow-up serum YKL-40 were detected by ELISA. We evaluated the association of YKL-40 with rapidly progressive interstitial lung disease (RPILD), severity of interstitial lung disease (ILD), and ILD-related survival. Forty-one out of 105 anti-MDA5+DM patients had RPILD at the time of serum sample collection (39.0%). Serum YKL-40 levels were significantly higher in anti-MDA5+DM patients with RPILD compared with those without (p = 0.011). One month after treatment, patients with aggravated ILD had increased YKL-40 levels, while those with stable/improved ILD had decreased YKL-40 levels. Higher serum levels of ferritin and YKL-40, as well as lower peripheral CD3+T cell counts, were independently associated with poorer prognosis. Kaplan-Meier survival curve showed that the 6months survival rate in patients with high serum YKL-40 level (> 80ng/ml) was significantly lower than that in patients with low YKL-40 level (≤ 80ng/ml) (67% vs 89%, p < 0.01). YKL-40 can be useful as an indicator for the occurrence of RPILD and correlates with severity of ILD and poor prognosis in anti-MDA5+DM patients. Closely monitoring and intensive treatment are suggested in anti-MDA5+DM patients showing high level of YKL-40, especially levels > 80ng/ml.

Yüksek serum YKL-40 düzeyi akciğer kanserinde kötü prognozla ilişkilidir

YKL-40 is a glycoprotein that plays role in inflammation and malignant processes. High serum YKL-40 levels are associated with short survive in cancer and chronic obstructive pulmonary disease (COPD) is another reason to increase its' level. However, limited knowledges are known in YKL-40 along with lung cancer and COPD. One hundred patients were involved to study with lung cancer (84 men, 16 women, and median age 62). Results were compared with 30 healthy volunteers. Thirteen patients were small cell lung cancer (SCLC), 87 patients were non-small cell lung cancer (NSCLC). 62% of patients were inoperable. Median YKL-40 level was 222.7 ± 114.1 ng/mL in patients and was 144.5 ± 105.7 ng/mL in controls (p< 0.001). Stage, tumour size, lymph node involvement and distant metastasis weren't associated with serum YKL-40 level. Above all cut-off values (133.159 and 162 ng/mL) survival was shorter (p> 0.05). Patients with COPD had worse survive above all cut-off values (p< 0.05), especially according to 133 ng/mL (p= 0.01). YKL-40 level is useful in lung cancer however it's not related to cell type and prognosis. It is associated with poor prognosis in lung cancer patients with COPD.

YKL-40 in the diagnosis, prediction of prognosis, and platinum sensitivity in serous epithelial ovarian cancer.

Objective:To evaluate the use of YKL-40 in the discrimination between benign and malignant adnexal mass and to determine its prognostic value in assessing residual tumor after primary cytoreduction and platinum sensitivity in serous epithelial ovarian carcinoma (EOC). Materials and Methods:During the three years from January 2015 to December 2017, a nonconsecutive series of 100 patient (60 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Preoperatively, serum samples were collected for YKL-40 level analysis.Results:YKL-40 [receiver operator characteristics (ROC)-area under curve (AUC)=0.83] was a significantly better predictor of EOC than cancer antigen-125 (ROC-AUC=0.75). Using a cut-off for YKL-40 of 47.7 ng/mL had a sensitivity of 80% and a specificity of 70%. Higher serum YKL-40 levels were associated with advanced stage, higher grade, residual tumor after primary cytoreduction and recurrence. Platinum-sensitive patients had significantly elevated levels of YKL-40 compared with platinum-resistant or refractory patients.Conclusion:The results obtained from our study support the use of serum YKL-40 for the discrimination between malignant and benign ovarian tumors. YKL-40 levels in patients with serous EOC may also predict disease residual disease after primary cytoreduction and recurrence. Further studies are needed to understand the relationship between YKL-40 and platinum sensitivity.

Combined Assessment of Serum Periostin and YKL-40 May Identify Asthma-COPD Overlap

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) has been proposed as a different diagnosis from asthma and COPD. However, little is known about the role of serum biomarkers in ACO. To evaluate serum periostin, a type 2 biomarker, and serum chitinase-3-like protein 1 (YKL-40), a useful biomarker for COPD, in Japanese patients with asthma, ACO, or COPD, and investigate the role of these biomarkers in identifying ACO. Subjects included Japanese patients with asthma (n= 177), ACO (n= 115), or COPD (n= 61). Serum periostin, YKL-40, and total IgE, blood eosinophils, and fractional exhaled nitric oxide were measured and compared among the patients. Serum periostin was high in both asthma and ACO, but not in COPD, whereas serum YKL-40 was high in both COPD and ACO, but not in asthma. Serum periostin levels correlated weakly with eosinophil counts in asthma, ACO, and COPD. Multivariate linear regression analysis revealed that older age, lower body mass index, higher eosinophil counts, higher total IgE, and the absence of the diagnosis of COPD were significantly associated with higher periostin levels. Based on cutoff values derived by receiver operating characteristic analysis (periostin: 55.1 ng/mL; YKL-40: 61.3 ng/mL), patients were classified into high or low groups. The proportion of patients with both high serum periostin and YKL-40 levels was significantly higher in ACO than in asthma or COPD. Serum periostin levels were comparable between asthma and ACO, whereas YKL-40 was comparable between ACO and COPD. Combined assessment of serum periostin and YKL-40 may identify ACO.

Characterisation of asthma subgroups associated with circulating YKL-40 levels.

The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups.Four YKL-40 clusters (C1-C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways.Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.

High serum YKL-40 level positively correlates with coronary artery disease.

We investigated the predictive value of chitinase-like protein YKL-40 in coronary artery disease (CAD). Serum YKL-40 levels in 116 CAD patients and 82 healthy controls were analyzed. Severity of CAD was evaluated using Gensini scores. Spearman's correlation was used to evaluate the correlation between Gensini scores and YKL-40 levels. The predictive value of YKL-40 was determined by receivers operating characteristic curve analysis. Serum YKL-40 levels were significantly elevated in CAD group as compared with control group. A positive correlation was found between the serum YKL-40 level and Gensini score. The optimum cut-off value of YKL-40 concentration was 127.7 ng/ml for distinguishing CAD patients from healthy controls with a 75.9% sensitivity and 57.3% specificity. A positive correlation exists between YKL-40 levels and CAD, and YKL-40 might be a useful adjunct in the diagnosis of CAD.

Evaluation of pleural fluid YKL-40 as a marker of malignant pleural effusion

The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types.The aim of this study is to assess pleural effusion and serum concentrations of YKL-40 in patients with different types of pleural effusions and to evaluate the diagnostic performance of YKL-40 in detecting malignant pleural effusion. Patients and methodsA prospective cohort study was carried out of 88 consecutive patients presenting with pleural effusions. The patients were divided into four groups: 22 patients with transudative effusions, 24 patients with parapneumonic pleural effusion and 8 patients with tuberculous pleural effusion and 34 patients with malignant pleural effusions. Blood and pleural fluid YKL-40 levels were measured using enzyme-linked immunosorbent assay. ResultsBoth serum HE4 levels and pleural effusion YKL-40 levels were significantly higher in patients with malignant effusions than in patients with transudative or non-malignant exudative effusions. A pleural fluid YKL-40 cut-off value of 256ng/mL was found to predict malignant pleural effusions with a diagnostic sensitivity of 85.3% and specificity of 90.7%. ConclusionThe current study reports a finding of increased serum and pleural fluid YKL-40 levels in patients with malignant pleural effusions compared to non-malignant effusions.

Elevated pretreatment serum concentration of YKL-40: an independent prognostic biomarker for poor survival in patients with colorectal cancer.

Serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL-40 and its relationship with colorectal cancer are poorly understood. Pretreatment serum levels of YKL-40 were determined in 86 patients with colorectal cancer and from 20 healthy controls. The serum YKL-40 levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum YKL-40 levels and clinicopathological findings and progression-free survival. Colorectal patients had a median serum YKL-40 level of 216 ng/mL (range 22.3-1, 253.2 ng/mL). Expression of serum YKL-40 levels was significantly higher in colorectal cancer patients compared with healthy controls, and the median serum values were 216 and 62.5 ng/mL, respectively (p < 0.01). No correlation was observed between progression-free survival and the type of chemotherapy regimen used tumor stage, sex, or histologic types. Patients with high serum YKL-40 levels [greater than the median level for all patients (216 ng/mL)] had a significantly shorter survival than patients with serum YKL-40 levels below the median (median progression-free survival, 36 vs. 50 months; p = 0.003). In multivariate analysis, the serum YKL-40 level, and the presence of distant metastasis were independent, statistically significant prognostic factors. The pretreatment serum YKL-40 level was identified as a new, independent prognostic biomarker in patients with colorectal cancer and may help to determine the individual prognosis of these patients.

YKL-40 expression in soft-tissue sarcomas and atypical lipomatous tumors

Background and purpose YKL-40 is a glycoprotein that is expressed in many types of cancer cells. In some cancers, there is a correlation between high serum YKL-40 levels on the one hand and more aggressive disease and early death on the other. YKL-40 has never been studied in patients with soft-tissue sarcomas (STSs). We investigated whether YKL-40 is expressed in STS tissue and ascertained that the degree of expression is related to survival and/or the histological grade of the malignancy (FNCLCC).Patients and methods We included archived tissue from 49 patients (40 with STS and 9 with atypical lipomatous tumor, 20 female and 29 male, mean age 58 (4–89) years) who were treated with tumor resection in 2004 or 2005 at the Department of Orthopedics, Rigshospitalet. The minimum length of follow-up with respect to survival was 5–7 years. Immunohistochemical analysis with anti-YKL-40 antibody using tissue microarray was performed on resected tumors, and a semiquantitative measure of the intensity of YKL-40 staining was performed.Results 41 of the 49 tumors were positive for YKL-40, and of these, 36 had moderate to intense staining. 24 of the patients died within the follow-up period, and the intensity of YKL-40 staining was significantly higher in tumors from patients who had died in the follow-up period than in tumors from those who survived (p = 0.01). The staining intensity was different for the 3 grades of malignancy (p = 0.004): it was higher in highly malignant tumors (FNCLCC grade 2 and grade 3) than in low-malignancy tumors (grade 1).Interpretation YKL-40 is expressed in soft-tissue sarcomas. There is a correlation between expression of YKL-40 in STS and both histological grade of the malignancy and survival. Whether or not YKL-40 expression is an independent prognostic variable could not be determined in the present study.

High Serum YKL-40 Level in Patients with COPD Is Related to Hypoxemia and Disease Severity

Chronic obstructive pulmonary disease (COPD) is a major health problem with increasing morbidity and mortality throughout the world. YKL-40 is a chitin-binding glycoprotein consisting of 383 amino acids, with a molecular mass of 40 kDa, and its serum level is elevated in inflammatory diseases. YKL-40 is a newly recognized biomarker of inflammation and has not been thoroughly investigated in COPD. The aim of the study is to investigate the relationship between serum YKL-40 levels and severity of COPD. The study population consisted of 52 patients with COPD with the mean age of 60.2 ± 10.1 years. The serum YKL-40 level increased significantly with increasing age (p = 0.022, r = 0.346). In COPD patients, high serum YKL-40 level is correlated to low forced expiratory volume at 1 second (FEV₁, percent of predicted) (r = -0.277, p = 0.047). Moreover, high serum YKL-40 level is correlated to low arterial oxygen pressure (PaO₂, mmHg) (r = -0.387, p = 0.005). The mean serum YKL-40 level was found as 243.1 ± 129.2 ng/ml in COPD patients with desaturation during 6-minute walk test (6MWT) and this value was higher than the mean serum YKL-40 level (155.8 ± 59.1 ng/ml) of COPD patients without desaturation during 6MWT (p = 0.004). This study demonstrated that high serum YKL-40 levels were correlated to severity of COPD. We propose that circulating YKL-40 levels could be a biomarker for hypoxemia and decline in lung function.

A promoter variant in the chitinase 3-like 1 gene is associated with serum YKL-40 level and personality trait

The chitinase 3-like 1 (CHI3L1) gene, a cellular survival factor against several environmental and psychosocial stresses, has been sown to be more highly expressed in the hippocampus and prefrontal cortex of patients with schizophrenia than unaffected individuals. We recently reported a significant association between schizophrenia and SNP rs4950928, which is located in the promoter region of the CHI3L1 gene, in a Japanese population. The G-allele at this SNP in the gene has been associated with higher transcriptional activity in a luciferase reporter assay and with higher mRNA levels in the peripheral blood cells of patients with schizophrenia. We investigated the impact of the CHI3L1 polymorphism rs4950928 on serum YKL-40 levels, the protein product of CHI3L1. We found that individuals with the G-allele, who were more prevalent among patients with schizophrenia, had significantly higher serum YKL-40 levels (p=0.043). Personality traits are considered to be an important aspect of schizophrenia primarily because they may influence symptoms and social functioning. Personality trait analyses using the temperament and character inventory (TCI) indicated that schizophrenic patients have a unique personality profile that appears to be present across cultures. We hypothesized that higher serum YKL-40 levels are associated with personality trait in patients with schizophrenia. Thus, we next examined the impact of the risk CHI3L1 polymorphism on personality traits using the TCI. We found that individuals with the G-allele had significantly higher self-transcendence scores (p=0.0054). These findings suggest possible associations between the SNP in the CHI3L1 gene, the risk for schizophrenia, and higher serum YKL-40 levels and personality traits in a Japanese population.

Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis

The chitinase-like protein YKL-40 is a serum biomarker in diseases with fibrosis, inflammation and tissue remodelling. Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that is hallmarked by these processes. The aim of this study was to investigate the potential of YKL-40 as a prognostic biomarker for survival in IPF patients. Serum and bronchoalveolar lavage fluid (BALF) levels of YKL-40 at the time of diagnosis and a promoter polymorphism in CHI3L1, the gene encoding YKL-40, were determined in 85 IPF patients and 126 controls. The relationship between YKL-40 levels and clinical parameters was evaluated. Kaplan-Meier and Cox regression analyses were used to examine the association between YKL-40 levels and survival. Serum and BALF YKL-40 levels were significantly higher in patients than in healthy controls (p<0.001). The -329 A/G polymorphism had a significant influence on BALF YKL-40 levels and the influence on serum YKL-40 levels showed a trend towards significance in IPF patients. IPF patients with high (>79ng/ml) serum or high BALF YKL-40 (>17ng/ml) levels had significantly shorter survival than those with low YKL-40 levels in serum or BALF. In patients with both low serum and low BALF YKL-40 levels no IPF related mortality was observed. Cox regression modelling showed that there were no confounding factors. The -329 polymorphism was associated with serum and BALF YKL-40 levels in IPF patients. High serum and BALF YKL-40 levels are associated with poor survival in IPF patients and could be useful prognostic markers for survival in IPF.

Elevated pretreatment serum concentration of YKL‐40—An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer

The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL-40 has not been established in nonsmall cell lung cancer (NSCLC). Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV disease. Ninety-eight patients received combined gemcitabine and vinorelbine, and 91 received combined gemcitabine, vinorelbine, and cisplatin as first-line chemotherapy. The median overall survival was 37 weeks. Patients had a median serum YKL-40 level of 209 ng/mL (range, 19-2153 ng/mL). No correlation was observed between overall survival and the type of chemotherapy regimen used, tumor stage, sex, or histologic types. Patients with high serum YKL-40 levels (greater than the median level for all patients [209 ng/mL]) had a significantly shorter survival than patients with serum YKL-40 levels below the median (median survival, 32 weeks vs 41 weeks; P = .007). In multivariate analysis, the serum YKL-40 level, the presence of bone lesions, and the serum lactate dehydrogenase level were independent, statistically significant prognostic factors. The pretreatment serum YKL-40 level was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients.

Serum levels of YKL-40 and interleukin-18 and their relationship to disease severity in patients with preeclampsia

Preeclampsia is a disease associated with the maternal inflammatory response. YKL-40 and interleukin-18 (IL-18) are inflammatory markers involved in inflammatory states and vascular processes. The aim of this study was to evaluate serum levels of YKL-40 and IL-18 in preeclampsia. Twenty-four patients with preeclampsia and 13 healthy pregnant women were included in this study. Serum levels of YKL-40 and IL-18 were measured using an enzyme-linked immunosorbent assay (ELISA). Serum YKL-40 levels were significantly higher in patients with preeclampsia (median 75.0 ng/mL; range 45.8–125.4 ng/mL) than in normal pregnant women (median 29.3 ng/mL; range 16.2–39.5 ng/mL; p = 0.000). Serum IL-18 levels were also significantly higher in patients with preeclampsia (median 159.9 pg/mL; range 125.6–193.5 pg/mL) than in normal pregnant women (median 120.2 pg/mL; range 102.2–157.9 pg/mL; p = 0.018). Notably, higher serum YKL-40 levels were observed in patients with more severe proteinuria (≥3+ by dipstick) than in patients with milder proteinuria (≤1+ by dipstick; median 121.3 ng/mL, range 63.5–146.7 ng/mL versus median 55.4 ng/mL, range 29.4–116.3 ng/mL; p = 0.022). There was, however, no significant difference in serum IL-18 levels between patients with more severe proteinuria and those with milder proteinuria. We conclude that circulating YKL-40 and IL-18 are elevated in patients with preeclampsia, and levels of YKL-40 are related to the severity of the disease.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer

YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer. YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths. The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 microg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05). Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.