MEX3A is a diagnostic, independent prognostic biomarker and a promising therapeutic target in glioblastoma

Lucia Di Marcotullio^1*Francesca Bufalieri¹Daniele Armocida²Antonino Cucinotta¹Pietro Familiari³Laura Di Magno¹Alessandra Serraino³Gennaro Adabbo¹Ludovica Lospinoso Severini¹Alessandro Frati³Gianluca Canettieri¹Paola Infante¹Antonio Santoro³Luca D'Angelo³

• ¹Department of Molecular Medicine, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy
• ²Mediterranean Neurological Institute Neuromed (IRCCS), Pozzilli, Italy
• ³Department of Human Neurosciences, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Lazio, Italy

Objective. Gliomas are the most common malignant brain tumors with a poor prognosis. Despite advances in molecular profiling, no targeted therapies significantly improve survival. Recently, it has been demonstrated that high expression of Muscle Excess 3A (MEX3A) correlates with poor overall survival (OS) in gliomas, generating interest in its potential as a biomarker and therapeutic target. This study analyzes the correlation between MEX3A expression and clinical-molecular features, assessing its diagnostic, prognostic, and therapeutic value in glioblastoma (GB), the most aggressive glioma subtype. Methods: We performed a retrospective study on a consecutive series of surgically-treated glioma patients. The values of MEX3A mRNA levels for the discrete variables examined has been reported by boxplots. Chi-square tests were carried out to analyze the correlation between MEX3A expression and patient features. Receiver operating characteristic (ROC) curve, Kaplan-Meier survival and Cox regression analysis were applied to assess the diagnostic and independent prognostic values of MEX3A in GB . Finally, the effect of MEX3A genetic knockdown on human primary GB both in vitro and in vivo orthotopic xenograft model cell has been evaluated. Results: Elevated MEX3A expression associates with more severe clinicopathological and molecular features of glioma patients. MEX3A exhibits high diagnostic accuracy (AUC > 0.9) and correlates with poor OS (HR=2.068, p=0.0018) and progression-free survival (PFS) (HR=2.209, p=0.0005) in GB. Multivariate Cox regression identified MEX3A as an independent prognostic factor for OS and PFS. Notably, MEX3A knockdown inhibits tumor growth in vitro and in vivo. Conclusions: Our findings highlight MEX3A as a novel diagnostic and prognostic biomarker and a promising therapeutic target for GB.