title: Layered signaling regulatory networks analysis of gene expression involved in malignant tumorigenesis of non-resolving ulcerative colitis via integration of cross-study microarray profiles.
abstract: BACKGROUND
  Ulcerative colitis (UC) was the most frequently diagnosed inflammatory bowel disease (IBD) and closely linked to colorectal carcinogenesis. By far, the underlying mechanisms associated with the disease are still unclear. With the increasing accumulation of microarray gene expression profiles, it is profitable to gain a systematic perspective based on gene regulatory networks to better elucidate the roles of genes associated with disorders. However, a major challenge for microarray data analysis is the integration of multiple-studies generated by different groups.
  
  
  RESULTS
  In this study, firstly, we modeled a signaling regulatory network associated with colorectal cancer (CRC) initiation via integration of cross-study microarray expression data sets using Empirical Bayes (EB) algorithm. Secondly, a manually curated human cancer signaling map was established via comprehensive retrieval of the publicly available repositories. Finally, the co-differently-expressed genes were manually curated to portray the layered signaling regulatory networks.
  
  
  RESULTS
  Overall, the remodeled signaling regulatory networks were separated into four major layers including extracellular, membrane, cytoplasm and nucleus, which led to the identification of five core biological processes and four signaling pathways associated with colorectal carcinogenesis. As a result, our biological interpretation highlighted the importance of EGF/EGFR signaling pathway, EPO signaling pathway, T cell signal transduction and members of the BCR signaling pathway, which were responsible for the malignant transition of CRC from the benign UC to the aggressive one.
  
  
  CONCLUSIONS
  The present study illustrated a standardized normalization approach for cross-study microarray expression data sets. Our model for signaling networks construction was based on the experimentally-supported interaction and microarray co-expression modeling. Pathway-based signaling regulatory networks analysis sketched a directive insight into colorectal carcinogenesis, which was of significant importance to monitor disease progression and improve therapeutic interventions.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Fan
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Pan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Geng
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yefan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Xuejun
authors.initials: X
authors.lastname: Li
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D019295:Computational Biology; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics*