Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Neurosurgery, Suining Central Hospital, Suining, China.
J Cell Biochem. 2019 Aug;120(8):12489-12499. doi: 10.1002/jcb.28515. Epub 2019 Feb 28.
Glioblastoma (GBM) is one of the most common highly malignant primary brain tumor with poor prognosis. This study aimed to explore the possible mechanism by bioinformatics method and detect potential function of UGP2 of GBM. Gene expression microarray data of GSE4412 and messenger RNA-sequencing data of GBM with samples clinical information were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas database, respectively. Differentially expressed genes (DEGs) analysis using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology based on R language. A total of 1000 common DEGs were identified in GBM samples, including 353 upregulated and 647 downregulated genes. Based on the random survival forest model, we identified UDP-glucose pyrophosphorylase 2 (UGP2) (upregulated gene) had a significant effect on GBM prognosis. Functional enrichment showed that UGP2 was enriched in the biological progresses of cell proliferation, migration, and invasion. Furthermore, UGP2 expression is aberrantly overexpressed in human glioma and positively correlated with pathologic grade. A loss-of-function study showed that knockdown of UGP2 decreases U251 cell growth, migration, and invasion in vivo and vitro. We proposed the development and progression of human glioma were associated with survival based on bioinformatics analysis. We also found that UGP2 might function as prognostic markers in the pathogenesis of GBM.
胶质母细胞瘤（GBM）是最常见的高度恶性原发性脑肿瘤之一，预后不良。本研究旨在通过生物信息学方法探讨其可能的机制，并检测 UGP2 在 GBM 中的潜在功能。从基因表达综合数据库和癌症基因组图谱数据库分别下载了 GBM 基因表达微阵列数据集（GSE4412）和信使 RNA 测序数据集，并附有样本临床信息。使用 R 语言基于京都基因与基因组百科全书和基因本体论进行差异表达基因（DEG）分析。在 GBM 样本中鉴定出了 1000 个共同的 DEG，包括 353 个上调基因和 647 个下调基因。基于随机生存森林模型，我们确定 UDP-葡萄糖焦磷酸化酶 2（UGP2）（上调基因）对 GBM 预后有显著影响。功能富集表明，UGP2 富集在细胞增殖、迁移和侵袭等生物学过程中。此外，人类神经胶质瘤中 UGP2 的表达异常上调，并与病理分级呈正相关。功能丧失研究表明，UGP2 的敲低可降低 U251 细胞在体内和体外的生长、迁移和侵袭能力。我们基于生物信息学分析提出了人类神经胶质瘤的发生和发展与生存有关。我们还发现 UGP2 可能在 GBM 的发病机制中作为预后标志物发挥作用。
