Analysis of the expression profile of Dickkopf-1 gene in human glioma and the association with tumor malignancy.

Abstract

BACKGROUND:

Gliomas represent the most common primary malignant brain tumors, yet little is known about the molecular pathogenesis of these tumors. The highly-regulated Wnt signal transduction pathway is essential for normal developmental processes, and defects in the pathway are closely linked to oncogenesis. Dickkopf-1 (DKK-1) is a secreted protein that acts as a potent inhibitor of the Wnt pathway. The aim of this study was to examine the expression profile of DKK-1 gene in human glioma and its association with tumor malignancy.

METHODS:

We determined the expression levels of DKK-1 transcript and protein in 12 glioblastoma cell lines, medulloblastoma cells, low-grade glioma cells, and human astrocyte cells by semiquantitative RT-PCR and ELISA. A total of 47 tumor biopsy specimens and 11 normal brain tissue samples from patients with cerebral trauma internal decompression were embedded in paraffin blocks and used for immunostaining. Twenty-six primary tumors and 7 corresponding brain samples were stored in liquid nitrogen and used for RT-PCR. We further examined serologic concentrations and cerebral fluid levels of DKK-1 in patients with tumors.

RESULTS:

DKK-1 could only be detected in 12 human glioblastoma cell lines, not in a panel of other tumor and normal cell lines. The difference between glioma patients and healthy individuals was significant. Kendall's tau-c association analysis also revealed the increased DKK-1 protein expression in tumor tissues of higher pathologic classification. The levels of cerebral fluid DKK-1 protein were significantly higher in glioma patients than in healthy donors or in neuronal benign tumor patients, suggesting that the DKK-1 molecule in cerebral fluids can be applicable to detect the presence of glioma and be developed as a novel prognostic treatment.

CONCLUSION:

The Wnt antagonist DKK-1 gene may have important roles in glioma tumorigenesis and act as a novel biomarker in human malignant glioblastoma.

• Authors: Youxin Zhou, Fang Liu, Qinian Xu, Xiuyun Wang
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 29 Pg. 138 (Oct 28 2010) ISSN: 1756-9966 [Electronic] England
• PMID: 21029453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• DKK1 protein, human
• Intercellular Signaling Peptides and Proteins

Topics

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Brain Neoplasms (genetics, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Gene Expression
• Gene Expression Profiling
• Glioma (genetics, metabolism, pathology)
• Humans
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Middle Aged
• Reverse Transcriptase Polymerase Chain Reaction
• Young Adult