ENTPD1 (CD39) and NT5E (CD73) expression in human Glioblastoma: an in silico analysis

Glioblastoma is the most common primary brain tumor in adults. It has a poor prognosis and the available lines of treatment have barely improved patient survival over the past decade. ENTPD1 and NT5E are genes that encode the cell surface enzymes CD39 and CD73, respectively. Both act in a purinergic extracellular pathway, hydrolyzing ATP into adenosine, promoting tumor immunosuppression, neovascularization and invasiveness. Thus, these genes emerge as genetic targets for new treatments for glioblastoma. We performed an in silico analysis of 156 tumor samples in an unexplored public database to investigate the prognostic value and consequent therapeutic potential for these genes. The analyzes revealed a significant increase in transcription levels of the genes under study in glioblastoma samples versus non-tumor brain tissue samples. High expression of NT5E or ENTPD1 is independently related to a decrease in overall survival (p = 5.4e-04, 1.1e-05). NT5E transcriptional levels are significantly higher in wild-type glioblastoma IDH patients compared to mutant glioblastoma IDH, while ENTPD1 levels show no significant differences, p ≤ 0.001. Finally, patients with mutated glioblastoma IDH and wild-type IDH had significantly lower overall survival when transcriptional levels of target genes were increased (p = 0.011; p = 3.2e-03). These data indicate the need for further population studies that explore the value of ENTPD1 and NT5E not only as prognostic markers but also as potential therapeutic targets.