Objective Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and based on cerebral imaging and histological examination. Serum based biomarkers may support detection of GBM. Here, we explored serum protein concentrations in GBM patients and used data mining to explore profiles of biomarkers and whether these associate with clinical status of the GBM patients. Methods Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differentially expressed in tumors versus normal brain tissues. The tumor expression and serum concentrations of 14 candidate proteins were analyzed in 23 GBM patients and 9 healthy subjects. Data mining methods involving all 14 proteins were applied as an initial evaluation step to find clinically informative profiles. Results Data mining identified a serum protein profile formed by BMP2, HSP70 and CXCL10 that allowed correct assignment into the GBM group with a specificity and sensitivity of 89% and 96%, respectively (p<0.0001, Fischer's exact test). Survival after tumor resection for more than 15 month was associated with a profile formed by TSP1, HSP70 and IGFBP3, allowing correct assignments in all cases (p<0.0001, Fischer's exact test). No correlation was found with tumor size and age of the patient. Conclusion The study shows that robust serum profiles for GBM may be identified by data mining based on a relatively small study cohort. Profiles of more than one biomarker allow a more specific assignment to the GBM and survival group than single proteins, confirming earlier attempts to correlate single markers with cancer. These findings will be a basis for validation in a larger sample size.

Glioblastoma multiforme are highly invasive brain tumors. Experimental approaches focus on unravelling the mechanisms of invasion, this being a major reason for the poor prognosis of these tumors. Our previous results hinted towards involvement of the iron metabolism in invasion. In this study, we examined the effect of iron depletion on the invasive phenotype of glioblastoma cells. Transwell Matrigel invasion assays were used to monitor iron-dependent invasion of human glioblastoma cell lines U373MG and DBTRG05MG. Intracellular iron concentrations were modulated by applying desferrioxamine (DFO) and ferric ammonium citrate (FAC). We detected enhanced invasion of glioblastoma cells upon DFO-induced iron depletion. Treatment of cells with FAC strongly inhibited invasion. DFO treatment resulted in hypoxia-inducible factor 1 (Hif-1)-mediated induction of urokinase plasminogen activator receptor and matrix metalloproteinase 2. Further, RNA interference-mediated repression of urokinase plasminogen activator receptor inhibited DFO-induced invasion. Our data demonstrate a direct effect of DFO on Hif-1 expression resulting in activation of factors associated with ECM degradation and invasion of glioma cells. These findings caution on utilization of DFO and other iron chelators in the treatment of tumors with invasive potential.

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