Modificazioni (epi)genetiche nella fisiopatologia dei tumori ipofisari: potenziali biomarker in ambito clinico e terapeutico

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). Purpose: In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profle with clinical and pathological features. Methods: Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA,n=12) and functioning (n=11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. Results: All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were signifcantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were diferentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p=0.036), miR-130a-3p (p=0.014), and miR-370-3p (p=0.026) were signifcantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p=0.031) and between miR-30a-5p and ‘atypical’ morphological features (p=0.038) or cavernous sinus invasion (p=0.049), while 508-5p was inversely correlated with clinical aggressiveness (p=0.043). Conclusions: In this study, we found a signifcant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profle related to functional status and tumor aggressiveness.