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 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.

中文翻译：

---

具有不同肿瘤等级的 MN1 过表达是神经胶质瘤患者生存的有希望的预测指标

摘要

神经胶质瘤具有相当大的死亡率与发病率之比和惨淡的临床病程。因此，更新的分子见解对于完善神经胶质瘤的诊断、预后和治疗势在必行。脑膜瘤 1 ( MN1 ) 基因是一种与其他恶性肿瘤有关的转录共调节因子，尽管其在胶质瘤病理学中的意义仍有待探索。IGFBP5受 MN1 和 IGF1 的转录调控，并且与较高的神经胶质瘤等级和较短的存活时间相关，促使我们确定它们在这些肿瘤中的相关性。我们量化了40 个神经胶质瘤样本中MN1、IGFBP5和IGF1的表达并检查了它们的相关性。MN1在这些肿瘤中评估了 mRNA-蛋白质的相互关系和基因的拷贝数。公开可用的 TCGA 数据集用于检查MN1表达水平与患者存活率的关联并验证我们的发现。我们观察到MN1过表达与低级别 (LGG) 而非高级别神经胶质瘤相关，并且不是由基因的拷贝数改变决定的。值得注意的是，MN1上调的胶质瘤具有更好的总生存期 (OS) 和无进展生存期 (PFS)。IGFBP5表达与胶质瘤中的MN1表达水平呈负相关，但与IGF1呈正相关仅在 LGG 中表达。这表明 MN1 和 IGF1 分别在IGFBP5的调节中的抑制和激活作用之间存在潜在的等级特异性相互作用。因此，MN1过表达是胶质瘤中 OS 和 PFS 的有希望预测因子，可作为临床实践中的预后生物标志物，对具有生存优势的患者进行分类。