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Upregulation of PAX3 confers a poor prognosis in Chinese glioblastoma patients with IDH1 wild type by increasing cell proliferation and migration

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机构: [1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China [2]China National Clinical Research Center for Neurological Diseases, Beijing, China [3]Department of Neurosurgery, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, China [4]Beijing Neurosurgical Institute, Beijing, China [5]Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
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关键词: IDH1 wild type glioblastoma PAX3 prognosis proliferation migration

摘要:
Glioblastoma multiforme (GBM) is a common lethal brain tumor. Genes involved in the pathogenesis of GBMs may have diagnostic value or be used as important prognostic factors. We have profiled whole genome mRNA expression array in 119 GBM patients and 5 normal brain tissues and transcriptome sequencing in 98 GBM patients from the Chinese Glioma Genome Atlas (CGGA) cohort to identify prognostic markers for GBM patients. Multivariate Cox proportional hazard regression analysis (p<0.01) and Significance Analysis of Microarrays (SAM, FDR<5%) were performed to identify prognostic genes in the GBMs group. Meanwhile, gene expression profile data of 196 GBMs from The Cancer Genome Atlas (TCGA) network was utilized to validate our results. Only genes significant in both CGGA and TCGA databases were chosen for further analysis. Kaplan-Meier survival analysis was performed to estimate overall survival of all GBM patients. PAX3 was identified as the most significantly prognostic gene using the above methods. Overexpression of PAX3 indicated poor survival in the 183 CGGA IDH1 wild type GBM patients but not in those of TCGA IDH1 wild type GBM patients. Prognostic value of PAX3 overexpression in GBMs was not interfered by clinicopathological features. Functional annotation of mRNA profiling and transcriptome data in GBMs from the CGGA and TCGA cohorts showed that patients with higher PAX3 expression tended to have a higher expression of proliferation associated genes. Knocking down the expression of PAX3 in U87 glioblastoma cells with PAX3 siRNA resulted in significant decrease in GBM cell proliferation and migration. The present study suggests that overexpression of PAX3 could be a marker with poor prognosis in IDH1 wild type GBMs by increasing cancer cell proliferation and migration.

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出版当年[2017]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验
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出版当年[2016]版:
Q4 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q4 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China [2]China National Clinical Research Center for Neurological Diseases, Beijing, China
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通讯作者:
通讯机构: [1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China [2]China National Clinical Research Center for Neurological Diseases, Beijing, China [5]Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China. [*1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantan Xili, Beijing 100050, China. [*2]Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, No.50 Xiangshan Yikesong Road, Beijing 100093, China.
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