The Influence of Distinct Regulatory miRNAs of the p15/p16/RB1/E2F Pathway on the Clinical Progression of Glioblastoma Multiforme

• Published in: World neurosurgery 2019-12, Vol.132, p.e900-e908
• Main Authors: Sippl, Christoph, Teping, Fritz, Ketter, Ralf, Braun, Luisa, Tremmel, Luisa, Schulz-Schaeffer, Walter, Oertel, Joachim, Urbschat, Steffi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Brain Neoplasms - genetics; Clinical; Cyclin-Dependent Kinase Inhibitor p15 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Disease Progression; DNA Methylation; E2F Transcription Factors - genetics; Epigenetic; Female; Gene Regulatory Networks; Glioblastoma - genetics; Glioblastoma multiforme; Humans; Male; microRNA; MicroRNAs - genetics; Middle Aged; Prognosis; Progression-Free Survival; Proportional Hazards Models; Retinoblastoma Binding Proteins - genetics; Signal Transduction; Ubiquitin-Protein Ligases - genetics
• ISSN: 1878-8750; 1878-8769
• DOI: 10.1016/j.wneu.2019.07.134

The microRNAs (miRNAs) -26a, -24, and -21 have been reported as regulators of the P15/P16/RB1/E2F pathway, which plays a major role in glioblastoma multiforme (GBM) progression. In the present study, their predictive marker for the progression of GBMs is evaluated and described. The expression of miRNA-21, -24, and -26a was analyzed as fold change (FC) in tumor specimens of 104 patients with GBM and 8 specimen of non-neoplastic brain tissue as control group. The results were referred to the individual clinical data sets and evaluated statistically. The FC of miRNA-21, -24, and -26a was 1.51 ± 1.35, 0.75 ± 0.67, and 0.39 ± 0.24 in the tumor samples. Within the control group, FC of miRNA-21, -24, and -26a was 0.31 ± 0.51, 0.66 ± 0.33, and 0.18 ± 0.11, respectively. MiRNA-26a and -21 were significantly overexpressed in GBM samples compared with healthy brain tissue (miRNA-21: P < 0.001; miRNA-26a: P = 0.011). High expression ofmiRNA-24 trended for a prolonged overall survival (P = 0.07). Patients with high miRNA-26a expression showed a significantly prolonged progression-free survival (hazard ratio 0.21; 95% confidence interval 0.09–0.51], P < 0.001) and overall survival (hazard ratio 0.3; 95% confidence interval 0.136–0.682], P = 0.003). The effect of miRNA-26a was mediated via regulation of mRNA of RB1. There was a significant inverse correlation between mRNA-26a and mRNA expression of RB1. The expression levels of miRNA-26a and -24 turned out to be promising predictors of further clinical course in patients with GBM multiforme.