Colombian Glioblastoma Patients Exhibit Age- and Proliferation- Associated miRNA Signatures Involving the miR-17-92 Cluster

Background: MicroRNA (miRNA) dysregulation plays a major role in glioblastoma (GBM) biology, but clinical implications are still incompletely defined. We conducted an exploratory miRNA profiling study of GBM in a Colombian cohort, associating molecular information with clinical characteristics. Methods: We retrospectively analyzed all adult patients treated surgically between 2015 and 2023 in two different institutions. Tumor samples were sequenced for small RNA. Associations with age, Ki67, and clinical variables were analyzed by differential miRNA expression analyses. Pathway enrichment using curated miRNA annotation databases was performed. Survival outcomes were evaluated using univariate Cox models. Results: 29 GBMs were included (23 histology grade 4; 6 molecularly reclassified grade 2–3). Increasing age correlated with downregulation of hsa-miR-17-5p and hsa-miR-92a-3p, while tumors with Ki67 ≥ 20% showed upregulation of hsa-miR-17-5p and hsa-miR-20a-5p, implicating the oncogenic miR-17-92 cluster in age- and proliferation-associated regulation. In the full cohort, only hsa-miR-31-5p had a significant correlation with overall survival. Pathway analyses revealed enrichment of miRNAs annotated to signaling pathways implicated in GBM biology. Conclusions: We identified age- and proliferation-associated miRNA patterns centered on the miR-17-92 cluster. The opposing regulation of this cluster with age (downregulation) versus high proliferative activity (upregulation), coupled with its lack of survival association, indicates that these patterns reflect underlying tumor biological heterogeneity rather than serving as prognostic biomarkers. These findings should be considered hypothesis-generating. Larger studies integrating molecular and surgical variables are necessary to establish the clinical utility of miRNA profiling in GBM