Bufalieri Francesca, Armocida Daniele, Cucinotta Antonino, Familiari Pietro, Di Magno Laura, Serraino Alessandra, Adabbo Gennaro, Agnoli Francesca, Lospinoso Severini Ludovica, Antonelli Manila, Frati Alessandro, Canettieri Gianluca, Infante Paola, Santoro Antonio, D'Angelo Luca, Di Marcotullio Lucia
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Experimental Neurosurgery Unit, IRCCS "Neuromed", Pozzilli, Italy.
Front Oncol. 2025 Sep 1;15:1585592. doi: 10.3389/fonc.2025.1585592. eCollection 2025.
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 expression and clinical-molecular features, assessing its diagnostic, prognostic, and therapeutic value in glioblastoma (GB), the most aggressive glioma subtype.
We performed a retrospective study on a consecutive series of surgically-treated glioma patients. The values of mRNA levels for the discrete variables examined has been reported by boxplots. Chi-square tests were carried out to analyze the correlation between 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 genetic knockdown on human primary GB both and orthotopic xenograft model cell has been evaluated.
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, knockdown inhibits tumor growth and
Our findings highlight MEX3A as a novel diagnostic and prognostic biomarker and a promising therapeutic target for GB.
胶质瘤是最常见的恶性脑肿瘤，预后较差。尽管在分子特征分析方面取得了进展，但尚无靶向治疗能显著提高生存率。最近，有研究表明，肌肉过量表达3A（MEX3A）的高表达与胶质瘤患者的总体生存率（OS）较差相关，这引发了人们对其作为生物标志物和治疗靶点潜力的兴趣。本研究分析了MEX3A表达与临床分子特征之间的相关性，评估其在最具侵袭性的胶质瘤亚型胶质母细胞瘤（GB）中的诊断、预后和治疗价值。
我们对一系列连续接受手术治疗的胶质瘤患者进行了回顾性研究。离散变量的mRNA水平值通过箱线图报告。进行卡方检验以分析MEX3A表达与患者特征之间的相关性。应用受试者工作特征（ROC）曲线、Kaplan-Meier生存分析和Cox回归分析来评估MEX3A在GB中的诊断和独立预后价值。最后，评估了MEX3A基因敲低对人原发性GB细胞系和原位异种移植模型细胞的影响。
MEX3A表达升高与胶质瘤患者更严重的临床病理和分子特征相关。MEX3A具有较高的诊断准确性（AUC>0.9），并且与GB患者的较差OS（HR=2.068，p=0.0018）和无进展生存期（PFS）（HR=2.209，p=0.0005）相关。多变量Cox回归确定MEX3A是OS和PFS的独立预后因素。值得注意的是，MEX3A敲低抑制肿瘤生长。
我们的研究结果突出了MEX3A作为一种新型诊断和预后生物标志物以及GB的有前景的治疗靶点。
