In glioblastoma metastasis, the malignant mGSC cells express markers of mesenchymal GSC subtype (MES-GSC), such as CD44 and YK-40 and their major obstacle seems to be propagating in the in various organs' microenvironments, different from the niches that home GSCs in the primary glioblastoma.
We also found that elevated serum/plasma YKL-40 had significant prognostic effects on OS in various cancer subgroups such as gastrointestinal tumors (HR, 1.37; 95% CI 1.18-1.58), ovarian cancer (HR, 2.27; 95% CI 1.69-3.06), melanoma (HR, 1.77; 95% CI 1.18-2.67), lung cancer (HR, 1.73; 95% CI 1.35-2.23), urologic neoplasms (HR, 1.61; 95% CI 1.08-2.40) and glioblastoma (HR, 1.23; 95% CI 1.07-1.42); in contrast, the prognostic effect of serum/plasma YKL-40 was not statistically significant in breast cancer (HR, 1.07; 95% CI 0.98-1.17).
In summary, the differential expression of the immunomodulatory molecule YKL-40 may affect the treatment efficacy of PI3K/AKT-based pathway inhibitors in glioblastoma.
Overall, this study identifies candidate changes in secreted proteins from NF1 deficient glioma cells that could influence the tumor microenvironment, and suggests a direct link between NF1 loss and increased tumor cell production of CHI3L1 and endoglin, two factors implicated in mesenchymal identity in glioblastoma.
We hypothesized that patients with newly diagnosed glioblastoma and low baseline plasma YKL-40 levels derive greater benefit from first-line bevacizumab.
Phospho-c-Jun activation by Anisomycin treatment in primary glioblastoma-derived cells attenuates the aggressive features of mesenchymal glioblastomas and leads to promoter methylation and downregulation of key mesenchymal genes (CD44, MMP9 and CHI3L1).
Meta-analysis of those studies showed that high YKL-40 expression was associated with worse overall survival in glioblastoma patients (HR = 1.46, 95%CI 1.33-1.61, P < 0.001).
Findings presented in our study showed that increased mRNA level of CHI3L1 could be associated with the progression of astrocytoma and poor patient survival not only for glioblastoma, but for lower grade astrocytoma tumors as well.
Both our case reports were adult males who developed extra-CNS, YKL-40-positive metastases at lymph nodes, lung and subcutaneous sites, after 86 and 24 months from initial diagnosis of GBM.
Therefore, YKL‑40 may be a novel key molecule in addition to MGMT, that is responsible for TMZ resistance in glioblastoma cell lines and could be a new target to overcome TMZ resistance in recurrent glioblastomas in the future.
In this paper, the authors' goal was to evaluate the prognostic value of YKL-40 expression as a prognostic factor for glioblastomas and to compare its validity to the already known MGMT.
Fitting models with and without YKL-40 highlights a subgroup of patients who have glioblastoma (GBM) diagnosis but appear to have better prognosis than the typical GBM patient.
Although YKL-40 expression is up-regulated in glioblastoma multiforme, its regulation and functions in nontransformed cells of the central nervous system are widely unexplored.
The objective of this study was to evaluate, in a series of 43 pediatric high-grade gliomas (21 anaplastic astrocytoma WHO grade III and 22 glioblastoma WHO grade IV), the prognostic value of histological grading and expression of p53 and YKL-40.
YKL-40 expression was higher in GBMs than AOs (P < 0.0001) and among GBMs, YKL-40 expression was lower in tumors with either EGFR amplification (P = 0.005) or elevated EGFR expression (P = 0.001).
High YKL-40 protein expression assessed by immunohistochemistry is found in breast carcinomas associated with short disease-free survival and in glioblastomas with increased resistance to radiotherapy and decreased overall survival.
Taken together our data suggest that the variant allele (-131C-->G) of CHI3L1 promoter has no significant impact on survival and is not a prognostic factor for glioblastoma.
YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization.