Feng Peng, Liu Shangyu, Yuan Guoqiang, Pan Yawen
The Second Medical College of Lanzhou University, Lanzhou, Gansu, 730030, PR China.
Department of Neurosurgery, Second Hospital of Lanzhou University, Lanzhou, Gansu, 730030, PR China.
Heliyon. 2024 Jul 4;10(15):e34119. doi: 10.1016/j.heliyon.2024.e34119. eCollection 2024 Aug 15.
The incidence of glioma, a prevalent brain malignancy, is increasing, particularly among the elderly population. This study aimed to elucidate the clinical importance of epithelial-mesenchymal transition (EMT) in gliomas and its association with malignancy and prognosis.
The incidence of glioma, particularly among elderly individuals, is on the rise. The malignancy of glioma is determined not only by the oncogenic properties of tumor cells but also by the composition of the tumor microenvironment, which includes immune system macrophages. The prevalence of M2-type macrophages typically fosters tumor progression, yet the underlying mechanism remains elusive. Our study explored the clinical importance of epithelial-mesenchymal transition (EMT) in gliomas and its association with malignancy and prognosis.
Our study used the gene set variation analysis (GSVA) algorithm to classify different levels of EMT activation based on the transcriptomic and multi-omics data. Machine learning (ML) and single-cell analysis were integrated into our model for comprehensive analysis. A predictive model was constructed and in vitro experiments were performed to validate our findings.
Our study classified 1,641 samples into two clusters based on EMT activation: the EMT-hot group and the EMT-cold group. The EMT-hot group had elevated copy number loss, tumor mutational burden (TMB), and a poorer survival rate. Conversely, the EMT-cold group showed a better survival rate, likely attributed to lower stromal and immune cell scores, as well as decreased expression of human leukocyte antigen-related genes. Driving genes were identified through weighted gene coexpression network analysis (WGCNA) and dimensionality reduction techniques. These genes were then utilized in the construction of a prognostic model using ML and protein-protein interaction (PPI) network analysis. Furthermore, the impact of the core genes identified through single-cell analysis on glioma prognosis was examined.
Our research underscores the efficacy of our model in predicting glioma prognosis and elucidates the connection between the M2 macrophages and EMT. Additionally, core genes such as LY96, C1QB, LGALS1, CSPG5, S100A8, and CHGB were identified as pivotal for mediating the occurrence of EMT induced by M2 macrophages.
神经胶质瘤是一种常见的脑部恶性肿瘤，其发病率正在上升，尤其是在老年人群中。本研究旨在阐明上皮-间质转化（EMT）在神经胶质瘤中的临床重要性及其与恶性程度和预后的关系。
神经胶质瘤的发病率，尤其是在老年人中，正在上升。神经胶质瘤的恶性程度不仅取决于肿瘤细胞的致癌特性，还取决于肿瘤微环境的组成，其中包括免疫系统巨噬细胞。M2型巨噬细胞的普遍存在通常促进肿瘤进展，但其潜在机制仍不清楚。我们的研究探讨了上皮-间质转化（EMT）在神经胶质瘤中的临床重要性及其与恶性程度和预后的关系。
我们的研究使用基因集变异分析（GSVA）算法，根据转录组学和多组学数据对不同水平的EMT激活进行分类。机器学习（ML）和单细胞分析被整合到我们的模型中进行综合分析。构建了一个预测模型，并进行了体外实验以验证我们的发现。
我们的研究根据EMT激活将1641个样本分为两个簇：EMT热组和EMT冷组。EMT热组的拷贝数缺失、肿瘤突变负担（TMB）升高，生存率较差。相反，EMT冷组的生存率较好，这可能归因于较低的基质和免疫细胞评分，以及人类白细胞抗原相关基因的表达降低。通过加权基因共表达网络分析（WGCNA）和降维技术确定了驱动基因。然后利用这些基因通过ML和蛋白质-蛋白质相互作用（PPI）网络分析构建预后模型。此外，还研究了通过单细胞分析确定的核心基因对神经胶质瘤预后的影响。
我们的研究强调了我们的模型在预测神经胶质瘤预后方面的有效性，并阐明了M2巨噬细胞与EMT之间的联系。此外，LY96、C1QB、LGALS1、CSPG5、S100A8和CHGB等核心基因被确定为介导M2巨噬细胞诱导EMT发生的关键基因。
