One of the most dramatically induced genes in GBM is
CHI3L1 [
13,
14]. A wealth of clinical evidence has also revealed that elevated serum levels of
CHI3L1 in GBM are positively correlated with cancer invasiveness, radioresistance, recurrence, and reduced patient survival times [
15]. There are data that,
CHI3L1 expression could be a prognostic predictor of glioblastoma [
5,
8,
16], although other studies have not supported this role [
17]. Pelloski with colleagues used subjective score (0, 1+, 2+) to evaluate CHI3L1 expression and found positive correlation between CHI3L1 staining and short survival [
18]. Later the same research group failed to find this correlation, but found that combined CHI3L1/EGFRvIII negative status was associated with better prognosis [
19]. In other studies was found no correlation between survival and CHI3L1 mRNA level [
16,
17]. Also no correlation was found between IHC staining for CHI3L1 and patient survival [
20]. Also, the literature up to date lacks crucial documentation of
CHI3L1 expression with respect to tumor grade and interface with survival. Recently, a number of gene expression array studies have identified
CHI3L1 to be one of the most overexpressed genes in glioblastoma when compared to low-grade glioma and normal brain [
13,
14,
21,
22], but most of them were carried out with small sample number. Either several medical and inflammatory diseases have been associated with elevated serum levels of YKL-40, including polycystic ovarian sindrome [
23], rheumatoid arthritis [
24], diabetes mellitus [
25]. These medical, inflammatory, and malignant diseases all possibly contribute to the levels of serum CHI3L1. In our study, we used real-time quantitative PCR (qRT-PCR) to measure the quantitative expression of
CHI3L1 in different grade astrocytoma tissues without the influence of other malignancies or medical diseases. Our data showed that
mRNA expression level of
CHI3L1 in glioma specimen was associated with tumour malignancy and patient overall survival. Higher mRNA level was more frequent in glioblastoma tissue as compared to grade II and III glioma. Grade I glioma also showed significantly higher
CHI3L1 mRNA expression as compared to grade II and III glioma, but less than GBM. It is important to mention that grade I glioma expression profile was more similar to healthy brain (RHB) sample and this could indicate that expression of
CHI3L1 is at very beginning stage of alteration in grade I glioma. This suggests that
CHI3L1 expression shifts through gliomagenesis and is downregulated at grade II and III but upregulated in GBM. Next it would be useful to find out what molecular mechanisms are responsible for this shifting, as far as this could be very important for tumour malignancy progression. The
CHI3L1 importance for gliomagenesis was showed by survival analysis. Despite grade I glioma specimen showed similar
CHI3L1 expression profile to glioblastoma specimen Kaplan-Meier curves strongly separate patient with different expression level to diverse survival groups. This demonstrates that
CHI3L1 mRNA expression level could be informative prognostic marker for glioma patient overall survival. Castells and colleagues reported that the expression values from only four transcripts (
CHI3L1,
LDHA,
LGALS1, and
IGFBP3) were able to distinguish two survival groups in Glioblastoma [
26]. Our findings propose that mRNA expression values of
CHI3L1, could be useful, not only for glioblastoma, but for lower grade astrocytoma diagnosis and prognosis too. Unlike
CHI3L1 mRNA data, promoter methylation status analysis did not reveal significant relevance on gliomagenesis. Such data could be clarified in two theories: wrong selection of gene promoter sequence to analyse; or different gene regulation mechanisms than promoter methylation is intrinsic for
CHI3L1. Recent discoveries found that CHI3L1 acts on glioblastoma-stem like cells (GSCs) to drive the formation of tumour vascularization and targeting CHI3L1 may compliment conventional anti-angiogenic therapies to provide a substantial clinical benefit to patients with GBM [
15].