521P - Deciphering a three-miRNA signature as a prognostic biomarker in glioma patients: Correlation with DFS and OS

Background

Gliomas are diffusely growing brain tumors and challenging cancers for diagnosis and treatment. The identification of genetic/epigenetic markers has changed glioma classification. Among the key genetic events, IDH mutations are noteworthy from a diagnostic and a prognostic point of view. MiRNAs are important players in glioma modulating cancer-related processes, including invasion and progression. We recently identified a serum diagnostic/prognostic miR-1, miR-26a-1 and miR-487b signature deregulated in glioma patients according to IDH mutation profile. We also found that this signature displays oncosuppressive functions with a marked inhibitory effect on migration and invasion by the direct targeting of crucial genes for invadopodia activity such as SH3PXD2B (miR-1), SH3PXD2A (miR-26a-1) and EFHD2 (miR-487b).

Methods

TCGA and CGGA databases were used to evaluate the correlation of the gene expression with glioma recurrence and Overall survival (OS). GSEA tool was used to identify pathways. Digital PCR and qRT-PCR were used to analyze miRNA and gene expression, respectively.

Results

In silico analyses show that the three-miRNA signature target genes were significantly downregulated in primary respect to recurrent patients. We also found that the combination of 2 out of 3 target genes is a strong prognostic biomarker. Median OS was 94.5 months in the Low-expression group versus 27.1 months in the High-expression group (HR=2.82[2.26-3.52], p=7.8e-20). These data were confirmed in a validation cohort. We also identified potential pathways deregulated in patients overexpressing the two genes and interestingly we found enriched pathways related to the immune system, angiogenesis and cell cycle. Our on-going experiments aim to validate experimentally the in silico data using a cohort of 80 glioma patients, including paired primary and recurrent tumor tissues.

Conclusions

The identification of a prognostic/predictive miRNA signature and its target genes, with a potential key role in glioma progression/recurrence through the regulation of important biological processes, could represent a step forward for the development of novel complementary therapies useful for patients management.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Italian Ministry of Health 'Starting Grant Bando Finalizzata 2021', Associazione Mia Neri Foundation supported by “Cassa Sovvenzioni e Risparmio Dipendenti Banca d’Italia”.

Disclosure

All authors have declared no conflicts of interest.