Zhang Yesen, Fan Huasheng, Zou Chun, Wei Feng, Sun Jiwei, Shang Yuchun, Chen Liechun, Wang Xiangyu, Hu Beiquan
Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, GD, China.
Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Front Genet. 2022 Aug 12;13:924802. doi: 10.3389/fgene.2022.924802. eCollection 2022.
Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Diagnostic and therapeutic challenges have been raised because of poor prognosis. Gene expression profiles of GBM and normal brain tissue samples from GSE68848, GSE16011, GSE7696, and The Cancer Genome Atlas (TCGA) were downloaded. We identified differentially expressed genes (DEGs) by differential expression analysis and obtained 3,800 intersected DEGs from all datasets. Enrichment analysis revealed that the intersected DEGs were involved in the MAPK and cAMP signaling pathways. We identified seven different modules and 2,856 module genes based on the co-expression analysis. Module genes were used to perform Cox and Kaplan-Meier analysis in TCGA to obtain 91 prognosis-related genes. Subsequently, we constructed a random survival forest model and a multivariate Cox model to identify seven hub genes (KDELR2, DLEU1, PTPRN, SRBD1, CRNDE, HPCAL1, and POLR1E). The seven hub genes were subjected to the risk score and survival analyses. Among these, CRNDE may be a key gene in GBM. A network of prognosis-related genes and the top three differentially expressed microRNAs with the largest fold-change was constructed. Moreover, we found a high infiltration of plasmacytoid dendritic cells and T helper 17 cells in GBM. In conclusion, the seven hub genes were speculated to be potential prognostic biomarkers for guiding immunotherapy and may have significant implications for the diagnosis and treatment of GBM.
胶质母细胞瘤（GBM）是成人中最常见且致命的原发性脑肿瘤。由于预后较差，诊断和治疗面临诸多挑战。我们下载了来自GSE68848、GSE16011、GSE7696和癌症基因组图谱（TCGA）的GBM和正常脑组织样本的基因表达谱。通过差异表达分析鉴定出差异表达基因（DEG），并从所有数据集中获得了3800个交集DEG。富集分析表明，交集DEG参与了MAPK和cAMP信号通路。基于共表达分析，我们鉴定出七个不同的模块和2856个模块基因。利用模块基因在TCGA中进行Cox和Kaplan-Meier分析，以获得91个与预后相关的基因。随后，我们构建了随机生存森林模型和多变量Cox模型，以鉴定七个核心基因（KDELR2、DLEU1、PTPRN、SRBD1、CRNDE、HPCAL1和POLR1E）。对这七个核心基因进行了风险评分和生存分析。其中，CRNDE可能是GBM中的关键基因。构建了与预后相关基因以及倍数变化最大的前三个差异表达微小RNA的网络。此外，我们发现GBM中浆细胞样树突状细胞和辅助性T细胞17有高度浸润。总之，推测这七个核心基因是指导免疫治疗的潜在预后生物标志物，可能对GBM的诊断和治疗具有重要意义。
