文章：

识别PLAUR作为肿瘤微环境的关键基因并调控胶质母细胞瘤间充质表型

Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma

原文发布日期：19 February 2024

DOI: 10.3390/cancers16040840

类型: Article

开放获取: 是

英文摘要：

The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand–receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.

摘要翻译： 

胶质母细胞瘤（GBM）的间充质（MES）表型是GBM中最具侵袭性和治疗抵抗性的亚型。肿瘤进展过程中的MES表型转变源于肿瘤内在的遗传改变和肿瘤外在的微环境因素。本研究旨在识别能够通过这两种机制调控MES表型的基因。通过整合加权基因共表达网络分析（WGCNA）与缺氧-免疫抑制相关基因的差异表达分析，我们鉴定出血浆纤溶酶原激活物、尿激酶受体（PLAUR）为核心基因。功能富集分析和GSVA分析表明，PLAUR与胶质瘤的MES表型以及缺氧-免疫抑制相关的微环境成分相关。单细胞测序分析揭示，PLAUR介导了肿瘤相关巨噬细胞（TAMs）与胶质瘤细胞之间的配体-受体相互作用。利用细胞系或原代胶质瘤细胞进行的体外功能实验，以及使用BALB/c裸鼠的异种移植模型，均证实了PLAUR在促进GBM的MES表型中的作用。我们的研究结果表明，PLAUR调控了有利于MES表型的胶质瘤细胞及肿瘤细胞外在因素，并提示PLAUR可能成为GBM治疗的潜在靶点。

原文链接：

Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma