Identification of Core Genes and Pathways in Medulloblastoma by Integrated Bioinformatics Analysis
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Identification of Core Genes and Pathways in Medulloblastoma by Integrated Bioinformatics Analysis Yuduo Guo 1 & Peng Huang 1 & Weihai Ning 1 & Hongwei Zhang 1 & Chunjiang Yu 1 Received: 10 February 2020 / Accepted: 13 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Medulloblastoma (MB) is one of the most common intracranial malignancies in children. The present study applied integrated bioinformatics to identify potential core genes associated with the pathogenesis of MB and reveal potential molecular mechanisms. Through the integrated analysis of multiple data sets from the Gene Expression Omnibus (GEO), 414 differentially expressed genes (DEGs) were identified. Combining the protein–protein interaction (PPI) network analysis with gene set enrichment analysis (GSEA), eight core genes, including CCNA2, CCNB1, CCNB2, AURKA, CDK1, MAD2L1, BUB1B, and RRM2, as well as four core pathways, including “cell cycle”, “oocyte meiosis”, “p53 pathway” and “DNA replication” were selected. In independent data sets, the core genes showed superior diagnostic values and significant prognostic correlations. Moreover, in the pan-caner data of the cancer genome atlas (TCGA), the core genes were also widely abnormally expressed. In conclusion, this study identified core genes and pathways of MB through integrated analysis to deepen the understanding of the molecular mechanisms underlying the MB and provide potential targets and pathways for diagnosis and treatment of MB. Keywords Medulloblastoma . Bioinformatics analysis . Differentially expressed genes . Pathways . GEO . TCGA
Introduction Medulloblastoma (MB) is one of the most common central nervous system (CNS) embryonic tumors in children and is highly invasive, accounting for 15–20% of pediatric CNS tumors (Gilbertson 2004; Bartlett et al. 2013). MBs are usually located in the posterior cranial fossa and cerebellum, and they tend to metastasize through the cerebrospinal fluid (CSF) during the early stages of the disease process (Northcott et al. 2012a). In 2016, based on molecular pathology, the World Health Organization (WHO) classified MB into four molecular types, including the WNT group, SHH group, group 3, and group 4 (Louis et al. 2016). The genetic events of WNT and Yuduo Guo, Peng Huang, Hongwei Zhang and Chunjiang Yu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-020-01556-1) contains supplementary material, which is available to authorized users. * Hongwei Zhang [email protected] * Chunjiang Yu [email protected] 1
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China
SHH groups mainly concentrate in WNT and SHH signaling pathways, respectively. APC and β-Catenin mutations have been widespread in the SHH group of MB (Northcott et al. 2017; Waszak et al. 2018). In the WNT subtypes, the deletion of PTCH1 and SUFU as well as GLI1/2 amplification involved in the WNT signaling pathway occur extensively
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