Zhang Lu-Yang, Guo Qing, Guan Ge-Fei, Cheng Wen, Cheng Peng, Wu An-Hua
Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
College of Applied Technology, China Medical University, Shenyang, China.
Front Oncol. 2019 Sep 20;9:904. doi: 10.3389/fonc.2019.00904. eCollection 2019.
Glioblastoma (GBM) is the most lethal cancer of the central nervous system. Integrin beta 5 () is thought to be involved in intercellular signal transduction and regulation of tumor initiation and progression. However, the function of in GBM is not known. To address this question, we evaluated the expression level of in clinical specimens by immunohistochemistry and western blotting, as well as the association between expression and GBM patient survival using data from Chinese Glioma Genome Atlas and The Cancer Genome Atlas. The biological function of in GBM was investigated by Gene Ontology, gene set enrichment, and loss-of-function experiments using glioma cells. Among integrin family members, showed the greatest difference in expression between low-grade glioma and GBM. Elevated ITGB5 expression was highly correlated with glioma progression and a mesenchymal subtype and poor survival in GBM patients. was found to be associated with regulation of the immune response and angiogenesis in GBM, and was required for migration and invasion of glioma cells and tube formation by endothelial cells. These data indicate that ITGB5 can serve as a predictive biomarker for GBM patient survival and is a potential therapeutic target in GBM treatment.
胶质母细胞瘤（GBM）是中枢神经系统中最致命的癌症。整合素β5（ITGB5）被认为参与细胞间信号转导以及肿瘤起始和进展的调控。然而，ITGB5在GBM中的功能尚不清楚。为了解决这个问题，我们通过免疫组织化学和蛋白质印迹法评估了临床标本中ITGB5的表达水平，并利用中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas）和癌症基因组图谱（The Cancer Genome Atlas）的数据研究了ITGB5表达与GBM患者生存之间的关联。我们通过基因本体论（Gene Ontology）、基因集富集分析以及使用胶质瘤细胞进行的ITGB5功能丧失实验，研究了ITGB5在GBM中的生物学功能。在整合素家族成员中，ITGB5在低级别胶质瘤和GBM之间的表达差异最大。ITGB5表达升高与胶质瘤进展、间充质亚型以及GBM患者的不良生存高度相关。研究发现ITGB5与GBM中的免疫反应调节和血管生成有关，并且是胶质瘤细胞迁移和侵袭以及内皮细胞形成血管管腔所必需的。这些数据表明，ITGB5可作为GBM患者生存的预测生物标志物，并且是GBM治疗中的潜在治疗靶点。
