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Midkine expression in high grade gliomas: Correlation of this novel marker with proliferation and survival in human gliomas.

ABSTRACT: BACKGROUND:High-grade primary glioma have poor prognosis and predictive biomarkers is very important. Midkine (MDK), a heparin-binding growth factor, is important in regulating carcinogenesis, cell proliferation, mitogenesis, and angiogenesis. This study aimed to identify over-expression of MDK in gliomas and correlate this with clinical outcomes. The authors put forward their hypothesis correlating proliferation and poor survival with over-expression of this novel protein. METHODS:Two datasets from Gene Expression Omnibus (GEO) included human data of 100 and 180 patients, respectively. The MDK expression, World Health Organization (WHO) pathological grade, sex, age, and survival time were identified for statistical analysis. RESULTS:A search of the GEO profile revealed that MDK expression level was statistically greater in the WHO grade IV compared with grade II (P = 0.002), in grades III and IV compared with nontumor control (P = 0.044 and P < 0.001, respectively) after adjustments using the Bonferroni method. By the Kaplan-Meier survival curve, the high MDK expression group had poorer survival outcome (2.38-fold hazard, 95% confidence interval: 1.22-4.63) than the low MDK expression group after adjustments for WHO grade and age. CONCLUSIONS:Taken together, there is a positive correlation between MDK expression and WHO grading of human gliomas. Moreover, MDK over-expression is significant correlated to poor survival outcome in high-grade, suggesting that MDK may be an important therapeutic target.

SUBMITTER: Cheng YP

PROVIDER: S-EPMC4061577 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Midkine expression in high grade gliomas: Correlation of this novel marker with proliferation and survival in human gliomas.

Cheng Yen-Po YP Lin Chin C Lin Ping-Yi PY Cheng Chun-Yuan CY Ma Hsin-I HI Chen Chien-Min CM Hueng Dueng-Yuan DY

Surgical neurology international 20140526

<h4>Background</h4>High-grade primary glioma have poor prognosis and predictive biomarkers is very important. Midkine (MDK), a heparin-binding growth factor, is important in regulating carcinogenesis, cell proliferation, mitogenesis, and angiogenesis. This study aimed to identify over-expression of MDK in gliomas and correlate this with clinical outcomes. The authors put forward their hypothesis correlating proliferation and poor survival with over-expression of this novel protein.<h4>Methods</h ...[more]

PMID: 24949221

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Project description:The outcome for children with high-grade gliomas (HGG) remains dismal, with a two-year survival rate of only 10-30%. Approximately half of pediatric HGGs are diffuse intrinsic pontine glioma (DIPG), a brainstem tumor that arises almost exclusively in children. Genome-wide analyses of copy number imbalances previously showed that platelet derived growth factor receptor alpha (PDGFRA) is the most frequent target of focal amplification in pediatric HGGs. To determine whether the PDGFRA is also targeted by more subtle mutations not detected by copy number analysis, we sequenced all PDGFRA coding exons from a cohort of pediatric HGGs. Somatic activating mutations were identified in 14.4% (13/90) of non-brainstem pediatric HGGs and 4.7% (2/43) of DIPGs, including missense mutations and in-frame deletions and insertions not previously described. 40% of tumors with mutation showed concurrent amplification, while 60% carried heterozygous mutations. Six different mutations impacting different domains all resulted in ligand-independent receptor activation that was blocked by small molecule inhibitors of PDGFR. Expression of mutants in p53-null primary mouse astrocytes conferred a proliferative advantage in vitro, and generated HGGs in vivo with complete penetrance when implanted into brain. The gene expression signatures reflected the spectrum of human diffuse HGGs. PDGFRA intragenic deletion of exons 8 and 9 were previously shown in adult HGG, but were not detected in 83 non-brainstem pediatric HGG and 57 DIPGs. Thus, a distinct spectrum of mutations confers constitutive receptor activation and oncogenic activity to PDGFR in childhood HGG. To better understand the consequence of PDGFRα mutation in pediatric gliomagenesis, retroviral constructs expressing wild-type PDGFRα or six selected PDGFRα mutants that affect different regions of the receptor were generated for functional studies. p53-null primary mouse astrocyte (PMA) cultures were chosen as a relevant cellular background to assess PDGFRα function.

Dataset Information

Midkine expression in high grade gliomas: Correlation of this novel marker with proliferation and survival in human gliomas.

Publications

Midkine expression in high grade gliomas: Correlation of this novel marker with proliferation and survival in human gliomas.

Similar Datasets

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