MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients

Gliomas are a type of human brain tumors that comprise <1.6% of all new cancer diagnoses worldwide. These tumors have a poor clinical prognosis, which is evident from the mortality to incidence rate ratio (MIR) of 0.80 as compared to say, breast (MIR 0.28) or prostrate cancer (MIR 0.26), thus being far more fatal than the latter two despite their significantly higher incidence rates. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. As a step in this direction we examined Meningioma 1 (MN1) gene, a transcriptional co-regulator, because it is implicated in different malignancies. Even though its significance in glioma pathology remains to be well elucidated, MN1 and other regulatory molecules such as insulin growth factor 1 (IGF1) modulate expression of insulin-like growth factor (IGF)-binding protein 5 (IGFBP5), which is associated with higher glioma grade and shorter survival span of patients. This prompted us to ascertain correlation between MN1, IGFBP5 and IGF1 in gliomas.

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. MN1 overexpression was correlated with low-grade (LGGs) and not high-grade gliomas (HGGs) and was not determined by the copy number alteration of the gene. Remarkably, gliomas with upregulated MN1 have better overall survival (OS) and progression-free survival (PFS). IGFBP5 expression associated inversely with MN1 expression 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 settings to categorize patients with survival advantage.

For full article: https://academic.oup.com/hmg/article-abstract/29/21/3532/5940464

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