National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad 121001, India.
Hum Mol Genet. 2021 Jan 6;29(21):3532-3545. doi: 10.1093/hmg/ddaa231.
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.
神经胶质瘤的死亡率与发病率之比相当高，临床病程较差。因此，为了完善神经胶质瘤的诊断、预后和治疗，需要更深入的分子研究。脑膜瘤 1 基因（MN1）是一种转录共调节因子，与其他恶性肿瘤有关，但其在神经胶质瘤发病机制中的意义仍有待探讨。IGFBP5 受 MN1 和 IGF1 的转录调控，与较高的神经胶质瘤分级和较短的生存时间相关，这促使我们在这些肿瘤中确定它们之间的相关性。我们定量检测了 40 例神经胶质瘤样本中 MN1、IGFBP5 和 IGF1 的表达，并研究了它们之间的相互关系。评估了这些肿瘤中 MN1 mRNA-蛋白的相关性及其基因的拷贝数。我们还使用了公共的 TCGA 数据集来研究 MN1 表达水平与患者生存的相关性，并验证了我们的发现。我们观察到 MN1 的过表达与低级别神经胶质瘤（LGGs）相关，而与高级别神经胶质瘤不相关，并且不受基因拷贝数改变的影响。值得注意的是，上调 MN1 的神经胶质瘤具有更好的总生存期（OS）和无进展生存期（PFS）。IGFBP5 在神经胶质瘤中的表达与 MN1 表达水平呈负相关，但仅在 LGGs 中与 IGF1 表达呈正相关。这表明 MN1 和 IGF1 分别在 IGFBP5 的调节中具有潜在的分级特异性相互作用，即抑制和激活作用。因此，MN1 的过表达是神经胶质瘤 OS 和 PFS 的一个有前途的预测因子，可能作为临床实践中的预后生物标志物，将具有生存优势的患者进行分类。
