Xu Libo, Wang Zhenhao, Li Mao, Li Qingsong
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
College of Biological Sciences, University of California, Davis, Davis, United States.
Front Oncol. 2025 Jul 7;15:1531937. doi: 10.3389/fonc.2025.1531937. eCollection 2025.
Glioblastoma (GBM) originates from neuroepithelial tissue and is one of the most common intracranial malignant tumors in adults, with high recurrence rate and poor prognosis. In recent years, SOX9 has been reported to play an important role in many diseases and cancers, and is a promising target, but it has been rarely reported in GBM.
RNA sequencing data of GBM were obtained from the Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database for analysis of SOX9 expression and differentially expressed genes (DEGs). Moreover, functional enrichment analysis of GBM-related DEGs was performed by GO/KEGG, GSEA, and protein-protein interaction (PPI) network. Additionally, the clinical significance of SOX9 in GBM was assessed by Kaplan-Meier Cox regression and prognostic model. What's more, we analyzed SOX9-related immune cell infiltration and expression of immune checkpoints in GBM. The incorporated studies were analyzed using the R package.
SOX9 was highly expressed in a range of malignant tumor tissues, including GBM. Surprisingly, high SOX9 expression was remarkably associated with better prognosis in the lymphoid invasion subgroups in a sample of 478 cases (P < 0.05). Totally, 126 differentially significant genes (DSGs) were identified between high- and low- expression group, of which 29 genes were upregulated and 97 genes were downregulated. Furthermore, high expression of SOX9 was an independent prognostic factor for IDH (isocitrate dehydrogenase)-mutant in Cox regression analysis. Screening was performed by LASSO coefficients to select non-zero variables that satisfied the coefficients of lambda. min, and four genes were screened out. OR4K2 and IDH status were prognostic factors associated with THCA in multifactorial COX regression analysis. SOX9, OR4K2 and IDH status were included in the nomogram prognostic model. Correlation analysis indicated SOX9 expression was correlated with immune cell infiltration and expression of immune checkpoints in GBM.
SOX9 was identified as a diagnostic and prognostic biomarker in glioblastoma, particularly in IDH-mutant cases. Its expression was closely correlated with immune infiltration and checkpoint expression, indicating its involvement in the immunosuppressive tumor microenvironment. SOX9-based gene signatures further supported a robust nomogram model, underscoring its potential as a therapeutic and prognostic target in GBM.
胶质母细胞瘤（GBM）起源于神经上皮组织，是成人最常见的颅内恶性肿瘤之一，复发率高且预后差。近年来，SOX9已被报道在许多疾病和癌症中发挥重要作用，是一个有前景的靶点，但在GBM中鲜有报道。
从癌症基因组图谱（TCGA）数据库和基因型-组织表达（GTEx）数据库获取GBM的RNA测序数据，用于分析SOX9表达和差异表达基因（DEGs）。此外，通过GO/KEGG、基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）网络对与GBM相关的DEGs进行功能富集分析。另外，通过Kaplan-Meier Cox回归和预后模型评估SOX9在GBM中的临床意义。此外，我们分析了GBM中与SOX9相关的免疫细胞浸润和免疫检查点的表达。使用R包对纳入的研究进行分析。
SOX9在包括GBM在内的一系列恶性肿瘤组织中高表达。令人惊讶的是，在478例样本的淋巴浸润亚组中，SOX9高表达与较好的预后显著相关（P < 0.05）。总共在高表达组和低表达组之间鉴定出126个差异显著基因（DSGs），其中29个基因上调，97个基因下调。此外，在Cox回归分析中，SOX9高表达是异柠檬酸脱氢酶（IDH）突变型的独立预后因素。通过最小绝对收缩和选择算子（LASSO）系数进行筛选，以选择满足lambda.min系数的非零变量，筛选出4个基因。在多因素COX回归分析中，嗅觉受体4K2（OR4K2）和IDH状态是与甲状腺癌（THCA）相关的预后因素。SOX9、OR4K2和IDH状态被纳入列线图预后模型。相关性分析表明，GBM中SOX9表达与免疫细胞浸润和免疫检查点的表达相关。
SOX9被确定为胶质母细胞瘤的诊断和预后生物标志物，特别是在IDH突变型病例中。其表达与免疫浸润和检查点表达密切相关，表明它参与免疫抑制性肿瘤微环境。基于SOX9的基因特征进一步支持了一个强大的列线图模型，突出了其作为GBM治疗和预后靶点的潜力。
