High Expression of FOXP2 Is Associated with Worse Prognosis in Glioblastoma

Abstract

Objective: FOXP2 expression has been associated with the prognosis of some tumors, but the role of FOXP2 in glioblastoma remains unclear. The aim of the present work is to study the role of FOXP2 as a prognostic biomarker in glioblastoma.

Methods: This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed both at protein level (immunohistochemistry, n = 62) and at mRNA level (RNAseq, in a cohort of glioblastoma patients from The Cancer Genome Atlas [TCGA] database, n = 148). Other molecular and clinical data have also been included in the study, with special focus on miRNA expression data. Survival analysis using log-rank test and COX-regression have been used. Non-parametric statistical tests were also used to study differences between low and high FOXP2 expression groups.

Results: Patients with a high expression of FOXP2 protein showed a worse prognosis than those patients with low expression in progression-free survival (hazard ratio 1.711; P = 0.034) and overall survival (hazard ratio 1.809; P = 0.014). These associations were still statistically significant in multivariate analysis. No prognostic association was found with FOXP2 RNA expression. Interestingly, 2 miRNAs that target FOXP2 (hsa-miR-181a-2-3p and hsa-miR-20a-3p) showed an interaction effect on overall survival with FOXP2 expression. A low level of these miRNA expression was associated with a significantly worse prognosis in patients with high FOXP2 RNA expression (log-rank test; P < 0.05).

Conclusions: Greater expression of FOXP2 at the protein level is associated with a worse prognosis. This protein expression may be regulated by the expression of specific miRNAs that target FOXP2 mRNA: hsa-miR-181a-2-3p and hsa-miR-20a-3p.

Keywords: Biomarker; FOXP2; Glioblastoma.