Background: Some evidence about the role of the androgen receptor (AR) in pathogenesis of glioblastoma have been reported, but no study has focused on measuring the activity of the AR in GB. Therefore, the aim of this work is to study the role of AR and its activity as prognostic biomarkers in glioblastoma (GB). Methods: Molecular and clinical data from The Cancer Genome Atlas database were used. The AR-expression at protein-level was obtained from reversed phase protein array (RPPA) assays. The AR-activity was determined by calculating the AR-score, an index calculated by using the expression (at RNA-level) of 13 androgen-responsive-genes. Univariate and multivariate Cox-regression analyses were performed. Finally, a correlation analysis was conducted between protein expression data and the AR-score. Results: Two-hundred and thirty-three patients were included. RPPA data showed a mean AR abundance of 0.027(Statistical Deviation = 0.38) in GB. The univariate Cox-regression analysis showed that the AR-Score was associated with a worse prognosis (Hazard Ratio (HR) = 1.070) while the AR-expression did not show any relationship with survival (HR = 0.869). The association of the AR-score with worse overall survival (OS) was still significant in the multivariate analysis (HR = 1.054). The highest correlation coefficients between the AR-score and RPPA were identified in a group of proteins involved in apoptotic process regulation. Conclusions: GB patients with a high AR-activity present a worse prognosis in terms of OS. Thus, the activity of the AR may have a pathogenic role in GB. In this regard, the activation of the AR in GB may be associated with a dysregulation of apoptosis.

No abstract

BACKGROUND Lung cancer (LC) is the second most frequent neoplasm worldwide and it is commonest origin of brain metastases (BM). The aim of this study is to identify clinical, histological and molecular variables associated with a higher risk of BM at diagnosis in LC patients. METHODS A retrospective single-centre case series analysis of patients with a new diagnosis of LC (from 2015 to 2018) was performed. A total of 723 newly diagnosed LC patients were identified and only those with a brain imaging study were included. Non-parametric statistical tests were used to compare patients with or without metastases at diagnosis. Uni- and multivariate analysis was performed to identify risk factors associated with the presence of BM. Statistical significance was considered when p<0.05. RESULTS 185 patients with newly diagnosed LC and brain imaging at diagnosis were included (mean age 64.69 years [SD= 10.34]; 71.9% male). 40% of patients had BM at diagnosis. No significant differences in clinical, histological and molecular variables were identified. In any case, survival analysis showed that BM at diagnosis was associated with worse overall survival (Log-Rank test, p<0.01). Univariate analysis showed that presenting neurological symptoms (OR=19.5, p<0.0001 CI [7.895-47.65]), adenocarcinoma (OR= 2.113, p<0.014 CI [1.160-3.849]), small cell carcinoma (OR=0.372, p<0.008 CI [0. 179-0.773]) and visceral metastases (OR= 14.444, p<0.0001 CI [6.161-33.86]) or metastases limited to the thorax (OR= 0.019, p<0.001 CI [0.003-0.146]) were associated with BM at diagnosis. However, only neurological symptoms (OR= 20.290, p<0.0001 CI [4.953-83.118]), visceral metastases (OR= 4.451, p<0.010 CI [1.458-13.777]) and/or metastases limited to the thorax (OR= 0.066, p<0.024 CI [0.006-0.010]) reached statistical significance in multivariate analysis. CONCLUSIONS Neurological symptoms and the presence of visceral metastases are independent predictors of developing BM at diagnosis in LC patients. However, LC disease confined to the thorax is associated with a lower risk of developing BM.

No abstract

FOXP2 expression has been associated with the prognosis of some tumors, but the role of FOXP2 in glioblastoma has not been studied in-depth until now. The aim of the present work is to study the role of FOXP2 as a prognostic biomarker in glioblastoma.This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed both at the protein level (immunohistochemistry) and at the mRNA level (RNAseq, in a cohort of glioblastoma patients from The Cancer Genome Atlas [TCGA] database). 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.Patients with a high expression of FOXP2 protein showed a worse prognosis than those patients with low expression in both, progression free survival (PFS) (HR=1.711; p=0.034) and overall survival (OS) (HR=1.809;p=0.014). These associations were still statistically significant in multivariate analysis.No prognostic association was found with FOXP2 RNA expression. Interestingly, two miRNAs that target FOXP2 (hsa-miR-181a-2-3p and hsa-miR-20a-3p) showed an interaction effect on OS with FOXP2 expression. A low level of these miRNAs expression was associated with a significantly worse prognosis in patients with high FOXP2 RNA expression.Higher 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.