Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma
Teng Deng, Yi-Zhen Gong, Xiang-Kun Wang, Xi-Wen Liao, Ke-Tuan Huang, Guang-Zhi Zhu, Hai-Nan Chen, Fang-Zhou Guo, Li-Gen Mo, Le-Qun Li
Department of Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
Med Sci Monit 2019; 25:3716-3727
The aim of this study was to identify gene signals for lower-grade glioma (LGG) and to assess their potential as recurrence biomarkers.
MATERIAL AND METHODS: An LGG-related mRNA sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA) Informix. Multiple bioinformatics analysis methods were used to identify key genes and potential molecular mechanisms in recurrence of LGG.
RESULTS: A total of 326 differentially-expressed genes (DEGs), were identified from 511 primary LGG tumor and 18 recurrent samples. Gene ontology (GO) analysis revealed that the DEGs were implicated in cell differentiation, neuron differentiation, negative regulation of neuron differentiation, and cell proliferation in the forebrain. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database suggests that DEGs are associated with proteoglycans in cancer, the Wnt signaling pathway, ECM-receptor interaction, the PI3K-Akt signaling pathway, transcriptional deregulation in cancer, and the Hippo signaling pathway. The hub DEGs in the protein-protein interaction network are apolipoprotein A2 (APOA2), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), tyrosinase (TYR), collagen type I alpha 2 chain (COL1A2), neurotensin (NTS), collagen type V alpha 1 chain (COL5A1), poly(A) polymerase beta (PAPOLB), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and anomalous homeobox (ANHX). GSEA revealed that the following biological processes may associated with LGG recurrence: cell cycle, DNA replication and repair, regulation of apoptosis, neuronal differentiation, and Wnt signaling pathway.
CONCLUSIONS: Our study demonstrated that hub DEGs may assist in the molecular understanding of LGG recurrence. These findings still need further molecular studies to identify the assignment of DEGs in LGG.
Keywords: Biological Markers, Brain Neoplasms, Glioma