An Integrated mRNA and microRNA Expression Signature for Glioblastoma Multiforme Prognosis

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures

Mitochondrial Alterations and Oxidative Stress in Cystic Fibrosis

Cystic fibrosis (CF) is the most frequent autosomal recessive disease and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Since the discovery of the deletion in the phenylalanine 508 site (ΔF508) of the CFTR gene, the study of its function as chloride channel occupied most investigations. Now, we know that CFTR is also involved in the GSH and HCO3− transport, and its function could regulate the mitochondrial function and ROS production. In this way, the notion of the CFTR as a simple chloride channel has begun to change toward a more complex function as molecular hub that integrates different cellular signals. There is a growing body of evidence that shows mitochondrial dysfunctions and increased oxidative stress in CF. Here, we review the mitochondrial defects induced by the altered function of the CFTR in CF, focusing on oxidative stress and inflammation as targets for therapy.Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin