Liu Erheng, Li Wenjuan, Jian Li-Peng, Yin Shi, Yang Shuaifeng, Zhao Heng, Huang Wei, Zhang Yongfa, Zhou Hu
Neurosurgery Department, The First People's Hospital of Yunnan Province.
Department of Chemical Biology, Yunnan Technician College, Kunming 650500, Yunnan, China.
Transl Oncol. 2023 Oct;36:101739. doi: 10.1016/j.tranon.2023.101739. Epub 2023 Aug 4.
Glioblastoma multiforme (GBM) is the most malignant type of glioma. GBM tumors grow rapidly, have a high degree of malignancy, and are characterized by a fast disease progression. Unfortunately, there is a lack of effective treatments. An effective strategy for the treatment of GBM would be to identify key biomarkers correlating with the occurrence and progression of GBM and developing these biomarkers into therapeutic targets.
In this study, using integrated bioinformatics analysis, we identified differentially expressed genes (DEGs), including 130 genes that were upregulated in GBM compared to normal brain tissue, and 128 genes that were downregulated in GBM. Based on Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, these genes were associated with regulation of tumor cell adhesion, differentiation, morphology in GBM and were mainly enriched in Complement and coagulation cascades pathway. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to construct a Protein-Protein Interaction network. Ten hub genes were identified, including FN1, CD44, MYC, CDK1, SERPINE1, COL3A1, COL1A2, LOX, POSTN and EZH2, all of which were significantly upregulated in GBM, these results were confirmed by oncomine database exploration. Alteration analysis of hub genes found that patients with alteration in at least one of the hub genes showed shorter median survival times (p = 0.013) and shorter median disease-free survival times (p = 2.488E-3) than patients without alterations in any of the hub genes. Multiple tests for survival analysis showed that among individual hub genes only expression of LOX was correlated with patient survival (P < 0.05).GDS4467 data set was used to analyze the expression of LOX in gliomas with different degrees of malignancy, and it was found that the expression level of LOX was positively correlated with the malignant degree of gliomas.By analyzing GDS 4535 data set showed that the expression level of LOX was positively correlated with the differentiation degree of GBM cells CONCLUSION: This research suggests that FN1, CD44, MYC, CDK1, SERPINE1, COL3A1, COL1A2, LOX, POSTN and EZH2 are key genes in GBM. However, only LOX is correlated with patient survival and promotes glioblastoma cell differentiation and tumor recurrence. LOX may be a candidate prognostic biomarker and potential therapeutic target for GBM.
多形性胶质母细胞瘤（GBM）是最恶性的胶质瘤类型。GBM肿瘤生长迅速，恶性程度高，疾病进展快。不幸的是，目前缺乏有效的治疗方法。治疗GBM的有效策略是识别与GBM发生和进展相关的关键生物标志物，并将这些生物标志物开发为治疗靶点。
在本研究中，我们使用综合生物信息学分析方法，鉴定了差异表达基因（DEG），其中包括与正常脑组织相比在GBM中上调的130个基因，以及在GBM中下调的128个基因。基于基因本体论富集分析和京都基因与基因组百科全书通路分析，这些基因与GBM中肿瘤细胞粘附、分化、形态的调控相关，主要富集于补体和凝血级联反应通路。使用检索相互作用基因的搜索工具（STRING）数据库构建蛋白质-蛋白质相互作用网络。鉴定出10个枢纽基因，包括FN1、CD44、MYC、CDK1、SERPINE1、COL3A1、COL1A2、LOX、POSTN和EZH2，所有这些基因在GBM中均显著上调，这些结果通过肿瘤在线数据库探索得到证实。枢纽基因的改变分析发现，至少有一个枢纽基因发生改变的患者的中位生存时间较短（p = 0.013），无病生存期的中位时间也较短（p = 2.488E-3），而没有任何枢纽基因改变的患者则不然。生存分析的多项检验表明，在单个枢纽基因中，只有LOX的表达与患者生存相关（P < 0.05）。使用GDS4467数据集分析不同恶性程度胶质瘤中LOX的表达，发现LOX的表达水平与胶质瘤的恶性程度呈正相关。通过分析GDS 4535数据集表明，LOX的表达水平与GBM细胞的分化程度呈正相关。结论：本研究表明，FN1、CD44、MYC、CDK1、SERPINE1、COL3A1、COL1A2、LOX、POSTN和EZH2是GBM中的关键基因。然而，只有LOX与患者生存相关，并促进胶质母细胞瘤细胞分化和肿瘤复发。LOX可能是GBM的候选预后生物标志物和潜在治疗靶点。
