title: Identification of hub genes and regulatory factors of glioblastoma multiforme subgroups by RNA-seq data analysis.
abstract: Glioblastoma multiforme (GBM) is the most common malignant brain tumor. This study aimed to identify the hub genes and regulatory factors of GBM subgroups by RNA sequencing (RNA-seq) data analysis, in order to explore the possible mechanisms responsbile for the progression of GBM. The dataset RNASeqV2 was downloaded by TCGA-Assembler, containing 169 GBM and 5 normal samples. Gene expression was calculated by the reads per kilobase per million reads measurement, and nor malized with tag count comparison. Following subgroup classification by the non-negative matrix factorization, the differentially expressed genes (DEGs) were screened in 4 GBM subgroups using the method of significance analysis of microarrays. Functional enrichment analysis was performed by DAVID, and the protein-protein interaction (PPI) network was constructed based on the HPRD database. The subgroup-related microRNAs (miRNAs or miRs), transcription factors (TFs) and small molecule drugs were predicted with pre-defined criteria. A cohort of 19,515 DEGs between the GBM and control samples was screened, which were predominantly enriched in cell cycle- and immunoreaction-related pathways. In the PPI network, lymphocyte cytosolic protein 2 (LCP2), breast cancer 1 (BRCA1), specificity protein 1 (Sp1) and chromodomain-helicase-DNA-binding protein 3 (CHD3) were the hub nodes in subgroups 1-4, respectively. Paired box 5 (PAX5), adipocyte protein 2 (aP2), E2F transcription factor 1 (E2F1) and cAMP-response element-binding protein-1 (CREB1) were the specific TFs in subgroups 1-4, respectively. miR‑147b, miR‑770-5p, miR‑220a and miR‑1247 were the particular miRNAs in subgroups 1-4, respectively. Natalizumab was the predicted small molecule drug in subgroup 2. In conclusion, the molecular regulatory mechanisms of GBM pathogenesis were distinct in the different subgroups. Several crucial genes, TFs, miRNAs and small molecules in the different GBM subgroups were identified, which may be used as potential markers. However, further experimental validations may be required.
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Yanan
authors: Y
authors: Li
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Weijie
authors: W
authors: Min
authors: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors: Mengmeng
authors: M
authors: Li
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Guosheng
authors: G
authors: Han
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Dongwei
authors: D
authors: Dai
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Xin
authors: X
authors: Chen
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Xinglai
authors: X
authors: Wang
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Yuhui
authors: Y
authors: Zhang
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Zhijian
authors: Z
authors: Yue
authors: Department of Neurosurgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors: Jianmin
authors: J
authors: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D060066:Protein Interaction Maps; D017423:Sequence Analysis, RNA / Q000379:methods*; D054852:Small Molecule Libraries / Q000494:pharmacology; D013223:Statistics as Topic; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D054852:Small Molecule Libraries; D014157:Transcription Factors