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Identifier 000439010
Title Molecular aspects of pediatric low-grade gliomas
Alternative Title Μοριακά δεδομένα στα χαμηλού βαθμού κακοήθειας γλοιώματα της παιδικής ηλικίας
Author Τσαούλη, Γεωργία
Thesis advisor Στειακάκη, Ευτυχία
Reviewer Ferretti, Elisabetta
Αγγελάκη, Σοφία
Abstract Pediatric low-grade gliomas (pLGGs) are a heterogeneous group of grade I and II glial tumors, whose mainstay of treatment is surgical resection. A subset of patients present tumor progression requiring adjuvant chemotherapy and/or radiotherapy, that often carry unsatisfactory results and long-term morbidity. Several studies have focused and clarified the genomic aspects of pLGGs. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet. Initially, we performed experiments based on previously published data that demonstrate the role of miR-139-5p in regulating PI3K/AKT signaling in supratentorial pLGGs. MiR- 139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signaling activation. Despite the progress in pLGG molecular characterization, up to date no biomarker predicting clinical outcome is available. For this purpose, microRNA profiles of 104 pLGG samples were collected from four European pediatric neuro-oncology centers and their microRNA profiles were analyzed. Low expression of miR-376a-3p and miR-888-5p was associated with tumor progression and poor overall survival. Expression levels of these microRNAs, according to enrichment analyses, were linked to tumor growth and cancer invasion pathways. These microRNAs might represent prognostic biomarkers able to stratify pLGG patients at the time of diagnosis. Additionally, the molecular aspects of these microRNAs could be significant for the identification of new target therapies.
Language English
Subject Biomarkers
Δυσμενής κλινική πορεία
Issue date 2021-03-29
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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