Protein and mRNA Levels of YKL-40 in High-Grade Glioma (original) (raw)
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Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas
Neuro-Oncology, 2011
The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P 5 .0008) and the glioblastoma (P 5 .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] 5 1.4, P 5 .01) and glioblastomas (HR 5 1.4, P < .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients.
Clinical Cancer Research, 2005
Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients (n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set (n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time ...
Clinical Cancer …, 2006
Biomarkers can facilitate diagnosis, monitor treatment response, and assess prognosis in some patients with cancer. YKL-40 and matrix metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed by malignant gliomas.We obtained prospective longitudinal serum samples from patients with gliomas to determine whether YKL-40 or MMP-9 could be used as serum markers. Experimental Design: Serum samples were obtained concurrently with magnetic resonance imaging scans. YKL-40 and MMP-9 were determined by ELISA and the values correlated with the patient's radiographic status and survival. Results: High-grade glioma patients who underwent a surgical resection of their tumor had transient increase of bothYKL-40 and MMP-9 serum levels in the postoperative period. Glioblastoma multiforme (GBM) patients with no radiographic evidence of disease (n = 10 patients, 50 samples) had a significantly lower level ofYKL-40 and MMP-9 than patients with active tumor (n = 66 patients, 209 samples; P = 0.0003 and 0.0002, respectively). Anaplastic glioma patients with no radiographic evidence of disease (n = 32 patients, 107 samples) also had a significantly lower level of YKL-40 compared with those patients with active tumor (n = 48 patients, 199 samples; P = 0.04). There was a significant inverse association between YKL-40 and survival in GBM, hazard ratio (hazard ratio, 1.4; P = 0.02), and anaplastic astrocytoma patients (hazard ratio, 2.2; P = 0.05). Conclusions: YKL-40 and MMP-9 can be monitored in patients' serum and help confirm the absence of active disease in GBM and YKL-40 in anaplastic glioma patients. YKL-40 can be used as predictor of survival in patients with high-grade glioma. Longitudinal studies with a larger patient population are needed to confirm these findings.
Overexpression of YKL-39 Gene in Glial Brain Tumors
Scholarly Research Exchange, 2008
More than forty genes with considerably increased expression in glioblastoma as compared to normal human brain were identified by SAGE. One of the most prominent among them was CHI3L2 (YKL-39) gene, which encodes 39 kDa chitinase-like protein. Northern blot hybridization confirmed the data of SAGE for the majority of glioblastomas. Anaplastic astrocytomas could be divided on two groups: in one of them the YKL-39 expression was completely undetectable, but in the other group quite high contents of YKL-39 mRNA were detected. In this study, preliminary data show that patients with undetectable expression of YKL-39 in anaplastic astrocytomas did not have recurrent tumors quite long (more than 2-3 years) period of time. YKL-39 RNA has not been detected in diffuse astrocytomas and in all (but one) samples of normal brain. Increased expression of YKL-39 gene in glioblastomas was shown also at the protein level. Western blots did not shown simultaneous production of YKL-39 and YKL-40, in spite of having high degree of their sequence identity. Increased expression of YKL-39 in subsets of patients with glial tumors, reported here for the first time, together with abnormal increase of the YKL-40 gene expression may be a novel molecular marker for glial tumors.
Role of YKL-40 in the Angiogenesis, Radioresistance, and Progression of Glioblastoma
Journal of Biological Chemistry, 2011
Glioblastoma is one of the most fatal cancers, characterized by a strong vascularized phenotype. YKL-40, a secreted glycoprotein, is overexpressed in patients with glioblastomas and has potential as a novel tumor biomarker. The molecular mechanisms of YKL-40 in glioblastoma development, however, are poorly understood. Here, we aimed to elucidate the role YKL-40 plays in the regulation of VEGF expression, tumor angiogenesis, and radioresistance. YKL-40 up-regulated VEGF expression in glioblastoma cell line U87, and both YKL-40 and VEGF synergistically promote endothelial cell angiogenesis. Interestingly, long term inhibition of VEGF up-regulated YKL-40. YKL-40 induced coordination of membrane receptor syndecan-1 and integrin ␣v5, and triggered a signaling cascade through FAK 397 to ERK-1 and ERK-2, leading to elevated VEGF and enhanced angiogenesis. In addition, ␥-irradiation of U87 cells increased YKL-40 expression that protects cell death through AKT activation and also enhances endothelial cell angiogenesis. Blockade of YKL-40 activity or expression decreased tumor growth, angiogenesis, and metastasis in xenografted animals. Immunohistochemical analysis of human glioblastomas revealed a correlation between YKL-40, VEGF, and patient survival. These findings have shed light on the mechanisms by which YKL-40 promotes tumor angiogenesis and malignancy, and thus provide a therapeutic target for tumor treatment. The abbreviations used are: Syn-1, syndecan-1; HMVECs, human microvascular endothelial cells; mAY, monoclonal anti-YKL-40 antibody; IHC, immunohistochemistry; Gy, gray.
Canadian Journal of Medicine, 2019
The prognosis of patients with malignant glioma is poor. Identification of novel and effective biomarkers for this purpose has long been an important target. In this study, we investigated the role and expression of GFAP, YKL-40 and RBP4 in glioma patients. We evaluated the expression of markers above on glioma by ELISA, qRT-PCR, Western blot, Kaplan-Meier method, log-rank test and Cox proportional-hazard analysis. The median RBP4 level in serum sample of patients was 53.61 ± 21.23 ng/ml, while it was 13.07 ± 10.31 ng/ml in control group. Moreover, the result revealed raised serum concentrations of YKL-40 and GFAP in patients as compared to controls. (The median level: 293.51± 105.41 versus 86.4 ± 51.2 ng/ml; 187.51± 91.06 versus 24.27 ± 12.64 ng/ml, respectively).And also, the transcriptional levels of RBP4 were determined to be increased in tumor tissue samples compared with control samples (mean ± SD: 2.82 ± 1.23 vs. 0.75 ± 0.21, P <0.001), as well as transcriptional levels YKL-40 and GFAP were notably strong in glioma patients, comparable to that seen in control tissues (mean ± SD: 5.33± 1.13 vs. 1.21 ± 0.86; 3.05± 1.37 vs. 0.68 ± 0.34; all P <0.001). Consistent with the transcriptional levels, western blotting analysis also indicated that the RBP4, YKL-40 and GFAP proteins were increased in glioma tissues. Furthermore, the serum RBP4 level was not linked to advanced tumor grade, age, location or gender or with Karnofsky performance Status (KPS) (all P >0.05). The serum YKL-40 and GFAP levels were significantly higher in glioma patients with high tumor grades (P= 0.001). The Kaplan-Meier analysis and the Log-rank test showed that high expression of YKL-40 and GFAP were associated with shorter survival (All p <0.001), while RBP4 expression was not related to shorter survival (P >0.05). Our results showed that high serum expression of YKL-40 and GFAP were independent prognostic molecule biomarkers for poor prognosis prediction in glioma patients.
A Comparative Study Of Lamps And Ykl-40 Tissue Expression In Glial Tumors
Folia Medica, 2014
INTRODUCTION: YKL-40 is a glycoprotein believed potentially to be a marker of various pathological processes. High levels of YKL-40 have been found in cancer and chronic infl ammatory diseases. The function of the glycoprotein is not completely known yet. A possible involvement in angiogenesis and tumor aggressiveness is supposed. Lysosome-associated membrane glycoproteins (LAMP) 1 and 2 are highly conserved proteins with still undefi ned biological functions. There is evidence that they are implicated in autophagy, angiogenesis and tissue remodeling. AIM: The aim of the present study was to investigate the potential relationship between the tissue expression of YKL-40, LAMP-1 and LAMP-2 in glial tumors. MATERIAL AND METHODS: LAMPs and YKL-40 expression was determined by immunohistochemistry in 36 glial tumors. A morphometric analysis of the intensity of tissue expression was performed with the Quick-photo Micro 2.3. system. Area (μm), perimeter (μm), and expression level (%) of the...
Folia Neuropathologica, 2017
Glioblastoma is the most common primary brain tumor. Despite multimodality therapy with aggressive microsurgical resection and adjuvant chemotherapy and radiotherapy, the median survival is below 15 months. Glioblastomas are heterogeneous tumors with high resistance to most chemotherapeutic drugs. According to reliable evidence, YKL-40, one of the best investigated chitinase-like protein, may facilitate invasion, migration and angiogenesis, and could be also responsible for temozolomide resistance in glioblastoma, thus conferring a dismal prognosis. Previous studies have demonstrated that glioblastoma stem cells give rise to endothelial cells through an YKL-40 influence. Such factor is closely related to the subventricular zone. This review focuses on the most recent theories involving the possible relationship between topographic gliomagenesis related to the subventricular zone and YKL-40.
Folia Neuropathologica, 2016
A b s t r a c t Glioblastomas (GBs) are the most common and lethal primary brain tumors in the adults. Glioblastomas originates either from astrocytes that have accumulated mutations and de-differentiated or from neural stem cells within the subventricular zone (SVZ) in close contact with the vasculature. Recently, several studies have hypothesized that gliomagenesis occurs in perivascular niches with highly invasive peripheral proliferating zones. The purpose of our study was to investigate the pathological and clinical significance of Olig2 and YKL40 immunoexpression in 152 GBs in relationship to the SVZ II and III. Olig2 expressions were successfully detected in 12 (15.58%) of 77 SVZ type II GBs and 16 (21.3%) of 75 SVZ type III GBs, respectively. YKL-40 expression was observed in 45 (58.4%) of 77 SVZ type II GBs and in 17 (22.6%) of 75 SVZ type III GBs, respectively. Stepwise multivariate Cox proportional hazards models were used, and the prognostic factors to significantly impact OS were: PFS < 54 weeks (HR: 5.86; CI: 3.02-11.33; p = 0.00); radiotherapy (HR: 0.34; CI: 0.18-0.60; p = 0.00); radio-and chemotherapy (HR: 0.05; CI: 0.03-0.10; p = 0.0), and YKL-40+ GBs (HR: 1.61; CI: 1.28-2.31; p = 0.01).
Serum YKL-40, A New Prognostic Biomarker in Cancer Patients?
Cancer Epidemiology Biomarkers & Prevention, 2006
YKL-40, a member of the ''mammalian chitinase-like proteins,'' is expressed and secreted by several types of solid tumors. The exact function of YKL-40 in cancer diseases is unknown and is an important objective of future studies. YKL-40 exhibits growth factor activity for cells involved in tissue remodeling processes. YKL-40 may have a role in cancer cell proliferation, survival, and invasiveness, in the inflammatory process around the tumor, angiogenesis, and remodeling of the extracellular matrix. YKL-40 is neither organ-nor tumor-specific. However, the present retrospective clinical studies of patients with eight different types of primary or advanced solid tumors suggest that serum concentration of YKL-40 may be a new biomarker in cancer patients used as a ''prognosticator.'' Elevated serum YKL-40 is found in a subgroup of patients with different types of solid tumors, including several types of adenocarcinomas, small cell lung carcinoma, glio-194