Supervisors info:
Καθηγητής Εμμανουήλ Καναβάκης, Επικ. Καθηγήτρια Μαρία Τζέτη, Καθηγητής Γεώργιος Χρούσος,
Summary:
Αlthough, substantial experimental evidence related to the diagnosis and
treatment of pediatric brain tumors has been demonstrated, the understanding of
the etiology and pathogenesis of the disease remains scarce. Recent microRNA
(miRNAs)-based research reveals the involvement of miRNAs in various aspects of
central nervous system development and proposes that they might compose key
molecules underlying oncogenesis. The current study evaluated the miRNA
differential expression detected between pediatric brain tumors and normal
tissue controls to characterize candidate biomarkers related to diagnosis,
prognosis and therapy. Overall, 19 resected tumors from children diagnosed with
brain tumor were studied. As controls, deceased children who underwent autopsy
and did not present any brain malignancy were used (n=4 samples of varying
localization). RNA extraction was carried out using the Trizol method, whilst
miRNA extraction was performed with the mirVANA miRNA isolation kit. The
experimental approach included microarrays covering 1211 miRNAs. The
multiparameter analyses were performed with MATLAB. For the analysis of
differentially expressed miRNA molecules, the bibliographic database Pubgene
was used among others, according to which correlations were found between
miRNAs and various diseases and molecular functional ontologies. As potential
diagnostic and prognostic markers, miR-130a and miR-943 were evaluated, whilst
miR-2355-5 emerged as a candidate biomarker for the early diagnosis of
malignancies related to favorable prognosis. In addition, miR-147, miR-409-3p,
miR-487b, miR-642b miR-874, miR-769-5p, miR-1267, miR-380, miR-3936 and miR-
483-3 could serve as significant prognostic markers, while miR-373, miR-508-3p,
miR-1197 and miR-218-1 might be used for generalised therapeutic approaches.
Finally, miR-155, miR-130a, miR-17, miR-136, miR-22, miR-224 and miR-23a were
evaluated as potential targets for individualized therapy. In conclusion,
deeper understanding of the aberrant miRNA expression in pediatric brain tumors
might aid in the development of tumor-specific miRNA signatures, which could
potentially afford promising biomarkers related to diagnosis, prognosis and
patient targeted therapy.
Keywords:
Brain tumors, Childhood, microRNAs, Prognostic markers, Therapeutic targets
