Abstract
INTRODUCTION
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumour in adults. Standard therapy, consisting in surgery followed by concomitant radio- and chemotherapy, only offers palliative benefits. Indeed, recurrence is inevitable and this disease remains incurable with an overall survival of 14.6 months. We believe that the chemoresistant phenotype of GBM is supported by their expression of several efflux pumps (ABC transporters). We thus hypothesized that gene expression of these transporters could correlate with patients clinical surrogates and be used as prognostic biomarkers.
RESULTS
We investigated the expression of ABCB1, ABCC1, ABCC3 and ABCG2 by qPCR in 159 GBM specimens collected during surgery and 22 non-tumoral brain tissue. With the exception of ABCB1, all three efflux pumps were significantly overexpressed in GBM. While ABCB1 had no effect on clinical surrogates, ABCC1 and ABCC3 expression correlated with drastically shorter overall survival (OS) and progression-free survival (PFS) in newly diagnosed patients. Moreover, our multivariate analysis showed that patients with high and moderate levels of ABCC3 had a considerably poorer prognosis than patients with low expressing tumours (hazard ratio [95% CI] was 2.424 [1.340 - 4.531]; p<0.001). However, in recurrent tumours, these transporters showed no correlation with clinical outcome. Interestingly, high ABCG2 expression correlated with better prognosis in both newly diagnosed and recurrent tumours (hazard ratio [95% CI] was 0.564 [0.323 - 0.986]; p=0.044).
CONCLUSION
This study shows that ABCC1, ABCC3 and ABCG2 transporters are upregulated in GBM tumours. Moreover, our data suggest that expression of these efflux pumps could be quantified upon diagnosis and serve as prognostic biomarkers for GBM patients. Therefore, we truly feel that ABCC1, ABCC3 and ABCG2 expression levels could be used to influence treatment and clinical management of patients.