Identification of two core genes in glioblastomas with different isocitrate dehydrogenase mutation status
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ORIGINAL ARTICLE
Identification of two core genes in glioblastomas with different isocitrate dehydrogenase mutation status Yuduo Guo1 · Xiang Wang1 · Weihai Ning1 · Hongwei Zhang1 · Chunjiang Yu1 Received: 20 June 2020 / Accepted: 3 September 2020 © Springer Nature B.V. 2020
Abstract Glioblastoma (GBM) is one of the most common malignancies of the central nervous system, and the Isocitrate Dehydrogenase (IDH) mutation status of GBM has been recognized as a critical prognostic indicator. However, the molecular mechanism underlying the GBM with different IDH mutation status is still not unclear. In this study, a total of 353 DEGs including 207 up-regulated and 146 down-regulated were screened from multiple GBM data sets. Moreover, the biological processes and pathways enriched by DEGs were mainly associated with tumor progression, especially invasion and migration. Then, eight hub genes, including SDC4, SERPINE1, TNC, THBS1, COL1A1, CXCL8, TIMP1 and VEGFA, were selected from a PPI network. Finally, core genes, SERPINE1 and TIMP1, were identified from hub genes by survival analysis and sample validation. Overall, in this study, we revealed underlying molecular mechanisms in GBMs with different IDH mutation status and identified core genes that could be potential markers and targets for diagnosis and treatment of GBMs. Keywords Glioblastoma · IDH mutation · Core genes · Pathways
Introduction Glioma is the most common primary tumor of the central nervous system (CNS) in adults [1]. Glioblastoma (GBM) is the most aggressive class of glioma with a median survival time of about 15 months despite advances in surgery, radiotherapy, and chemotherapy [2, 3]. Moreover, decades of research for improving the prognosis of GBM is disappointing [4, 5]. The main reason that restricts the effect of treatment is the inherent heterogeneity of GBM [6, 7]. Therefore, for more accurate diagnosis and treatment, in 2016, the World Health Organization (WHO) introduced molecular classification into the guideline for tumors of Hongwei Zhang and Chunjiang Yu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05804-w) contains supplementary material, which is available to authorized users. * Chunjiang Yu [email protected] 1
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, No. 50, Xiangshan Yikesong Road, Haidian District, Beijing 100093, People’s Republic of China
CNS [8]. According to the mutation status of the Isocitrate Dehydrogenase gene (IDH), GBM is classified into three subtypes, including IDH-wildtype, IDH-mutant, and NOS (not otherwise specified) [8]. The IDH-mutant GBM has a favorable prognosis compared with IDH-wildtype GBM [9, 10]. Additionally, some studies reported that IDH mutation is an early event of glioma, which has fundamental significance for the progress and biological behavior of glioma [11, 12]. And, GBMs with different IDH mutation status retain differences in the molecular mechanism. A
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