title: Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.
abstract: The molecular mechanism underlying tumor-induced epileptogenesis is poorly understood. Alterations in the peritumoral microenvironment are believed to play a significant role in inducing epileptogenesis. We hypothesize that the change of gene expression in brain peritumoral tissues may contribute to the increased neuronal excitability and epileptogenesis. To identify the genes possibly involved in tumor-induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from formalin-fixed paraffin embedded (FFPE) peritumoral cortex tissue slides from 5-seizure vs. 5-non-seizure low grade brain tumor patients. We identified many differentially expressed genes (DEGs). Seven dysregulated genes (i.e., C1QB, CALCRL, CCR1, KAL1, SLC1A2, SSTR1 and TYRO3) were validated by qRT-PCR, which showed a high concordance. Principal Component Analysis (PCA) showed that epilepsy subjects were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy subjects. Molecular functional categorization showed that significant portions of the DEGs functioned as receptor activity, molecular binding including enzyme binding and transcription factor binding. Pathway analysis showed these DEGs were mainly enriched in focal adhesion, ECM-receptor interaction, and cell adhesion molecules pathways. In conclusion, our study showed that dysregulation of gene expression in the peritumoral tissues may be one of the major mechanisms of brain tumor induced-epilepsy. However, due to the small sample size of the present study, further validation study is needed. A deeper characterization on the dysregulated genes involved in brain tumor-induced epilepsy may shed some light on the management of epilepsy due to brain tumors.
authors: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors: Charles E
authors: CE
authors: Niesen
authors: Jun
authors: J
authors: Xu
authors: Xuemo
authors: X
authors: Fan
authors: Xiaojin
authors: X
authors: Li
authors: Christopher J
authors: CJ
authors: Wheeler
authors: Adam N
authors: AN
authors: Mamelak
authors: Charles
authors: C
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics*; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D004827:Epilepsy / Q000209:etiology / Q000235:genetics*; D027342:Excitatory Amino Acid Transporter 2; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D025341:Principal Component Analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D054389:Receptors, CCR1 / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C076266:ANOS1 protein, human; C087299:C1QBP protein, human; C545578:CALCRL protein, human; C515300:CCR1 protein, human; D058286:Calcitonin Receptor-Like Protein; D002352:Carrier Proteins; D027342:Excitatory Amino Acid Transporter 2; D016326:Extracellular Matrix Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D054389:Receptors, CCR1; D017481:Receptors, Somatostatin; C493397:SLC1A2 protein, human; C101130:somatostatin receptor type 1; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human