title: Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development.
abstract: BACKGROUND
  A large number of gene expression profiling (GEP) studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis.
  
  
  METHODS
  We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9%) had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO) categories or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration.
  
  
  RESULTS
  Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities.
  
  
  CONCLUSIONS
  We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jesús
authors.initials: J
authors.lastname: Lascorz
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Asta
authors.initials: A
authors.lastname: Försti