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Malignant gliomas constitute a complex disease phenotype that demands optimum decision-making as they are highly heterogeneous. Such inter-individual variability also renders optimum patient stratification extremely difficult. microRNA (hsa-miR-20a, hsa-miR-21, hsa-miR-21) expression levels were determined by RT-qPCR, upon FFPE tissue sample collection of glioblastoma multiforme patients (n = 37). In silico validation was then performed through discriminant analysis. Immunohistochemistry images from biopsy material were utilized by a hybrid deep learning system to further cross validate the distinctive capability of patient risk groups. Our standard-of-care treated patient cohort demonstrates no age- or sex- dependence. The expression values of the 3-miRNA signature between the low- (OS > 12 months) and high-risk (OS < 12 months) groups yield a p-value of 12 months) vs. high-risk (OS < 12 months) glioblastoma multiforme patients. Our 3-microRNA signature (hsa-miR-20a, hsa-miR-21, hsa-miR-10a) may further empower glioblastoma multiforme prognostic evaluation in clinical practice and enrich drug repurposing pipelines.