title: Ranking candidate genes of esophageal squamous cell carcinomas based on differentially expressed genes and the topological properties of the co-expression network.
abstract: BACKGROUND
  The aim of this study was to identify the candidate genes of esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Gene expression profiling of 17 ESCC samples and 17 adjacent normal samples, GSE20347, was downloaded from Gene Expression Omnibus database. The raw data were preprocessed, and the differentially expressed genes (DEGs) between ESCC and normal samples were identified by using SAM software (false discovery rate <0.001). Then, the co-expression network of DEGs was constructed based on Pearson's correlation test (r-value ≥0.8). Furthermore, the topological properties of the co-expression network were analyzed through NetworkAnalyzer (default settings) of Cytoscape. The expression fold changes of DEGs and topological properties were utilized to identify the candidate genes of ESCC (Crin score >4), which were further analyzed based on DAVID functional enrichment analysis (P-value <0.05).
  
  
  RESULTS
  A total of 1,063 DEGs were identified, including 490 up-regulated and 573 down-regulated DEGs. Then, the co-expression network of DEGs was constructed, containing 999 nodes and 46,323 edges. Based on the expression fold changes of DEGs and the topological properties of the co-expression network, DEGs were ranked, and the top 24 genes were candidate genes of ESCC, such as CRISP3, EREG, CXCR2, and CRNN. Furthermore, the 24 genes were significantly enriched in bio-functions regarding cell differentiation, glucan biosynthetic process and immune response.
  
  
  CONCLUSIONS
  The present study suggested that CRISP3, EREG, CXCR2, and CRNN might be causative genes of ESCC, and play vital roles in the development of ESCC. However, further experimental studies are needed to confirm our results.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Shen
authors.forename: Jicheng
authors.initials: J
authors.lastname: Tantai
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D066260:Epiregulin / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies / Q000145:classification*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis; D029589:Seminal Plasma Proteins / Q000096:biosynthesis
chemical_list: C489926:CRISP3 protein, human; C418764:CRNN protein, human; C587880:EREG protein, human; D066260:Epiregulin; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D023063:Receptors, Interleukin-8B; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins