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

Abstract

Gliomas 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 MN1, IGFBP5 and IGF1 expression in 40 glioma samples and examined their interrelatedness. MN1 mRNA-protein inter-correlation and 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 (HGGs), and is not determined by copy number alteration of the gene. Notably, gliomas with upregulated MN1 have better overall and progression-free survival. IGFBP5 expression inversely associated 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 overall and progression-free survival in gliomas, may serve as a prognostic biomarker in clinical practice to categorize patients with survival advantage.

Prognostic and Predictive Biomarkers in Gliomas

“…Meningioma 1 ( MN1 ) gene is a transcriptional co-regulator located on chromosome 22q [ 115 , 116 ]. Alterations in MN1 frequently occur in astroblastoma, a type of gliomas.…”

“…MN1 is a positive prognostic factor [ 115 , 116 ]. Gliomas with upregulated MN1 have better OS and PFS [ 116 ].…”

“…MN1 is a positive prognostic factor [ 115 , 116 ]. Gliomas with upregulated MN1 have better OS and PFS [ 116 ]. According to Lehman et al MN1 rearranged astroblastomas were associated with a favorable prognosis which was mainly in comparison to BRAF V600E-mutated pleomorphic xanthoastrocytoma [ 118 ].…”

Mutational profiling of low‐grade gliomas identifies prognosis and immunotherapy‐related biomarkers and tumour immune microenvironment characteristics

“…22 WHO grades I and II are classified as LGG, while the other two grades III and IV are classified as high-grade glioma (HGG). 23 LGG was characterized by slow progress and malignant transformation potential. 5 Virtually, all LGG finally will be malignantly transformed to HGG.…”

“…Gliomas were classified in four grades according to clinicopathological and histological features by the WHO 22 . WHO grades I and II are classified as LGG, while the other two grades III and IV are classified as high‐grade glioma (HGG) 23 . LGG was characterized by slow progress and malignant transformation potential 5 .…”