title: Identifying key stage-specific genes and transcription factors for gastric cancer based on RNA-sequencing data.
abstract: BACKGROUND
  To identify gastric cancer (GC)-associated genes and transcription factors (TFs) using RNA-sequencing (RNA-seq) data of Asians.
  
  
  METHODS
  The RNA-seq data (GSE36968) were downloaded from Gene Expression Omnibus database, including 6 noncancerous gastric tissue samples, 5 stage I GC samples, 5 stage II GC samples, 8 stage III GC samples, and 6 stage IV GC samples. The gene expression values in each sample were calculated using Cuffdiff. Following, stage-specific genes were identified by 1-way analysis of variance and hierarchical clustering analysis. Upstream TFs were identified using Seqpos. Besides, functional enrichment analysis of stage-specific genes was performed by DAVID. In addition, the underlying protein-protein interactions (PPIs) information among stage IV-specific genes were extracted from STRING database and PPI network was constructed using Cytoscape software.
  
  
  RESULTS
  A total of 3576 stage-specific genes were identified, including 813 specifically up-regulated genes in the normal gastric tissues, 2224 stage I and II-specific genes, and 539 stage IV-specific genes. Also, a total of 9 and 11 up-regulated TFs were identified for the stage I and II-specific genes and stage IV-specific genes, respectively. Functional enrichment showed SPARC, MMP17, and COL6A3 were related to extracellular matrix. Notably, 2 regulatory pathways HOXA4-GLI3-RUNX2-FGF2 and HMGA2-PRKCA were obtained from the PPI network for stage IV-specific genes. In the PPI network, TFs HOXA4 and HMGA2 might function via mediating other genes.
  
  
  CONCLUSIONS
  These stage-specific genes and TFs might act in the pathogenesis of GC in Asians.
authors.affiliation: Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D016000:Cluster Analysis; D024142:Collagen Type VI / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D025743:HMGA2 Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000378:metabolism; D009367:Neoplasm Staging; D015676:Osteonectin / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C000601102:COL6A3 protein, human; D024142:Collagen Type VI; D025743:HMGA2 Protein; D018398:Homeodomain Proteins; D015676:Osteonectin; C577241:SPARC protein, human; D014157:Transcription Factors; C073547:HOXA4 protein, human; C402225:MMP17 protein, human; D053504:Matrix Metalloproteinases, Membrane-Associated