Department of Neurobiology, School of Medicine, South China University of Technology, Guangzhou, China.
Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Exp Cell Res. 2024 Jun 1;439(1):114076. doi: 10.1016/j.yexcr.2024.114076. Epub 2024 May 7.
Glioblastoma (GBM) is a common primary central nervous system tumor. The molecular mechanisms of glioma are unknown, and the prognosis is poor. Therefore, exploring the underlying mechanisms and screening for new prognostic markers and therapeutic targets is crucial. We utilized the weighted gene co-expression network analysis (WGCNA), Differentially Expressed Genes (DEGs), and LASSO-COX analysis to identify three target genes. Next, we constructed and evaluated a prognostic model, screening out COL8A1 as a risk gene. Through a sequence of cellular functional experiments, in vivo studies, and RNA sequencing, we delved into exploring the functional effects and molecular mechanisms of COL8A1 on GBM cells. Finally, the correlation between COL8A1 and tumor immune cells and different inflammatory responses was analyzed. Immunohistochemistry experiments revealed the influence of COL8A1 on macrophage polarization. The COL8A1 expression level was associated with the grade, prognosis, and tumor microenvironment (TME) of glioma. Functional experiments showed that COL8A1 inhibited GBM cell apoptosis and promoted migration, invasion, and proliferation in vitro and in vivo. We also found that COL8A1 promotes the epithelial-mesenchymal transition process and may mediate the activation of the ERK pathway through SHC1. In addition, immune infiltration analysis showed that COL8A1 was closely associated with macrophages in glioma tissues, significantly suppressing the signaling of M1-like -type macrophages and enhancing the signaling of M2-like -type macrophages. COL8A1 was first found to be associated with prognosis, progression, and immune microenvironment of glioma and may serve as a new marker of prognosis and a therapeutic target.
胶质母细胞瘤（GBM）是一种常见的原发性中枢神经系统肿瘤。目前尚不清楚胶质瘤的分子机制，且预后较差。因此，探索潜在的机制，筛选新的预后标志物和治疗靶点至关重要。我们利用加权基因共表达网络分析（WGCNA）、差异表达基因（DEGs）和 LASSO-COX 分析鉴定出三个靶基因。接下来，我们构建并评估了一个预后模型，筛选出 COL8A1 作为风险基因。通过一系列细胞功能实验、体内研究和 RNA 测序，深入探讨了 COL8A1 对 GBM 细胞的功能影响和分子机制。最后，分析了 COL8A1 与肿瘤免疫细胞和不同炎症反应的相关性。免疫组织化学实验揭示了 COL8A1 对巨噬细胞极化的影响。COL8A1 的表达水平与胶质瘤的分级、预后和肿瘤微环境（TME）有关。功能实验表明，COL8A1 抑制 GBM 细胞凋亡，并促进体外和体内迁移、侵袭和增殖。我们还发现 COL8A1 促进上皮-间充质转化过程，并可能通过 SHC1 介导 ERK 通路的激活。此外，免疫浸润分析表明，COL8A1 与胶质瘤组织中的巨噬细胞密切相关，显著抑制 M1 样巨噬细胞的信号，并增强 M2 样巨噬细胞的信号。COL8A1 首次被发现与胶质瘤的预后、进展和免疫微环境有关，可能成为新的预后标志物和治疗靶点。
