Dottorato in MEDICINA MOLECOLARE

Titolo della tesi: The role of MEX3A in glioma as a biomarker and prognostic marker

Abstract Background: Gliomas are the most common primary brain tumor often associated with treatment resistance and poor prognosis. Gliomas engage various mechanisms to promote its progression and among these, the post-transcriptional factors with a deregulated expression of non-coding RNAs having been implicated in onset, progression, invasiveness, and recurrence. MEX3A participates in the degradation or inhibition of mRNA by ubiquitination and various studies provided evidence that it plays an important role in the occurrence and development of gliomas. However, at present there are no in vivo studies that correlate MEX3A expression with the clinical and molecular characteristics of diagnosed gliomas. Methods: We performed an observational study of a consecutive series of surgically treated patients suffering from intracranial brain tumors, with the aim to analyze the expression of MEX3A in glioma cells and its correlations with clinical and molecular aspects. Results: The final cohort consisted in 76 patients with histologically diagnosed glioma, 46 males and 30 females. We identified a positive correlation with age, namely that patients over 64 years old had higher MEX3A expression (27/44, 61.3%, p=0.028). We found the correlation with EGFR expression where 17/27 patients (63%) had high expression of MEX3A. Mex3A also appears to be significantly related to tumor grading (p=0.05) and cell replication index identified as ki67 % expression where for values above 20% there was high expression (24/41 patients, 59%, p=0.02). Conclusions: Our study highlights the relationship between MEX3A expression with clinical and molecular characteristics of a large series of glioma-patients, identifying how its expression correlates closely with patient age, tumor grading, cell replication index, and EGFR expression, suggesting its role as a tumor marker and negative prognostic factor.