MN1overexpression with varying tumor grade is a promising predictor of survival of glioma patients

Abstract

AbstractGliomas have substantial mortality to incidence rate ratio and a dismal clinical course. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. Meningioma 1 (MN1) gene is a transcriptional co-regulator implicated in other malignancies, albeit its significance in glioma pathology remains to be explored. IGFBP5 is regulated transcriptionally by MN1 and IGF1 and is associated with higher glioma grade and shorter survival time, prompting us to ascertain their correlation in these tumors. We quantified the expression of MN1, IGFBP5 and IGF1 in 40 glioma samples and examined their interrelatedness. MN1 mRNA-protein inter-correlation and the gene’s copy number were evaluated in these tumors. Publicly available TCGA datasets were used to examine the association of MN1 expression levels with patient survival and for validating our findings. We observed MN1 overexpression correlated with low-grade (LGGs) and not high-grade gliomas and is not determined by the copy number alteration of the gene. Notably, gliomas with upregulated MN1 have better overall survival (OS) and progression-free survival (PFS). IGFBP5 expression associated inversely with MN1 expression levels in gliomas but correlated positively with IGF1 expression in only LGGs. This suggests a potential grade-specific interplay between repressive and activating roles of MN1 and IGF1, respectively, in the regulation of IGFBP5. Thus, MN1 overexpression, a promising predictor of OS and PFS in gliomas, may serve as a prognostic biomarker in clinical practice to categorize patients with survival advantage.