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Stem cell associated gene expression in glioblastoma multiforme: relationship to survival and the subventricular zone
Melanie Kappadakunnel1, Ascia Eskin, Jun Dong
1University of California Los Angeles, Los Angeles, CA 90095, USA.
Abstract:
Current therapies for glioblastoma (GBM) target bulk tumor through measures such as resection and radiotherapy. However, recent evidence suggests that targeting a subset of tumor cells, so-called cancer stem cells, may be critical for inhibiting tumor growth and relapse. The subventricular zone (SVZ), which lines the ventricles of the brain, is thought to be the origin for the majority of neural stem cells and potentially cancer stem cells. Therefore, we assessed the relationship between tumor contact with the SVZ as determined by MRI, cancer stem cell gene expression and survival in 47 patients with GBM. Using DNA microarrays, we found that genes associated with cancer stem cells were not over-expressed in tumors contacting the SVZ. Contact with the SVZ trended with shorter survival (median 358 versus 644, P = 0.066). Over-expression of CD133 (prominin-1) and maternal embryonic leucine zipper kinase (MELK) was associated with shorter survival, whereas mitogen activated protein kinase 8 (MAPK8) was associated with longer survival (P values 0.008, 0.005 and 0.002 respectively). Thus we found no evidence of a stem-cell derived genetic signature specific for GBM in contact with the SVZ, but there was a relationship between stem cell gene expression and survival. More research is required to clarify the relationship between the SVZ, cancer stem cells and survival.
Insights
Glioblastoma tumors touching the brain's subventricular zone (SVZ) did not show stem cell gene over-expression but trended toward shorter survival. Specific gene markers, like CD133 and MELK, impacted patient outcomes.
Area of Science:
- Neuro-oncology
- Cancer Stem Cell Biology
- Molecular Genetics
Background:
- Glioblastoma (GBM) therapies often target bulk tumor cells.
- Cancer stem cells (CSCs) are implicated in GBM growth and relapse.
- The subventricular zone (SVZ) is a potential origin for neural stem cells and CSCs.
Purpose of the Study:
- To investigate the relationship between GBM tumor contact with the SVZ, CSC gene expression, and patient survival.
- To determine if SVZ contact correlates with specific CSC genetic signatures.
- To identify prognostic gene markers in GBM related to CSCs.
Main Methods:
- Magnetic Resonance Imaging (MRI) to assess tumor contact with the SVZ in 47 GBM patients.
- DNA microarray analysis to evaluate gene expression, focusing on CSC-associated genes.
- Statistical analysis to correlate SVZ contact, gene expression patterns, and patient survival data.
Main Results:
- No significant over-expression of CSC-associated genes was found in GBM tumors contacting the SVZ.
- Tumor contact with the SVZ showed a trend towards shorter patient survival (P=0.066).
- Over-expression of CD133 and MELK genes correlated with shorter survival; MAPK8 correlated with longer survival (P<0.01).
Conclusions:
- The study found no distinct CSC-derived genetic signature in GBM tumors adjacent to the SVZ.
- A correlation exists between CSC gene expression profiles and glioblastoma patient survival.
- Further research is needed to elucidate the complex interplay between the SVZ, CSCs, and GBM prognosis.
