title: Unique genome-wide map of TCF4 and STAT3 targets using ChIP-seq reveals their association with new molecular subtypes of glioblastoma.
abstract: BACKGROUND
  Aberrant activation of beta-catenin/TCF4 and STAT3 signaling in glioblastoma multiforme (GBM) has been reported. However, the molecular mechanisms related to this process are still poorly understood.
  
  
  METHODS
  Genome-wide screening of the binding characteristics of the transcription factors TCF4 and STAT3 in GBM cells was performed by chromatin immunoprecipitation sequencing (ChIP-seq) assay. Hierarchical clustering was used to analyze the association of TCF4 and STAT3 coregulated genes with The Cancer Genome Atlas (TCGA) GBM subtypes (classical, mesenchymal, neural, and proneural). New molecular classification of GBM was proposed and validated in Western and Asian populations.
  
  
  RESULTS
  We identified 1250 overlapping putative target genes that were coregulated by TCF4 and STAT3. Further, the coregulated genes had the potential to guide TCGA GBM subtypes. Finally, we proposed a new molecular classification of GBM into 2 subtypes (proneural-like and mesenchymal-like) and showed that the new classification could be applied to both Western and Asian populations. In addition, the GBM response to temozolomide therapy differed depending on its subtype; mesenchymal-like GBM benefited, while there was no benefit for proneural-like GBM.
  
  
  CONCLUSIONS
  This is the first comprehensive study to combine a ChIP-seq assay of TCF4 and STAT3 and data mining of patient cohorts to derive molecular subtypes of GBM.
authors.affiliation: Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Xiao
authors.initials: X
authors.lastname: Yue
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: You
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Pu
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015894:Genome, Human; D005909:Glioblastoma / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors