Systematic identification of core transcription factors mediating dysregulated links bridging inflammatory bowel diseases and colorectal cancer

PLoS One. 2013 Dec 26;8(12):e83495. doi: 10.1371/journal.pone.0083495. eCollection 2013.

Abstract

Accumulating evidence shows a tight link between inflammation and cancer. However, comprehensive identification of pivotal transcription factors (i.e., core TFs) mediating the dysregulated links remains challenging, mainly due to a lack of samples that can effectively reflect the connections between inflammation and tumorigenesis. Here, we constructed a series of TF-mediated regulatory networks from a large compendium of expression profiling of normal colonic tissues, inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), which contains 1201 samples in total, and then proposed a network-based approach to characterize potential links bridging inflammation and cancer. For this purpose, we computed significantly dysregulated relationships between inflammation and their linked cancer networks, and then 24 core TFs with their dysregulated genes were identified. Collectively, our approach provides us with quite important insight into inflammation-associated tumorigenesis in colorectal cancer, which could also be applied to identify functionally dysregulated relationships mediating the links between other different disease phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Transformation, Neoplastic / genetics*
  • Cluster Analysis
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics*
  • Computational Biology / methods
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / genetics*
  • Models, Biological
  • Transcription Factors / genetics*

Substances

  • Transcription Factors

Associated data

  • GEO/GSE3629
  • GEO/GSE8671

Grants and funding

This work was supported in part by the Creative Research Groups of The National Natural Science Foundation of China (grant numbers 81121003, 91129710, 91029717, 91229112 and 31200997), the Specialized Research Fund for the Doctoral Program of Higher Education of China (grant number 20102307110022), the Science Foundation of Heilongjiang Province (grant numbers D200834 and C201207) and the Science Foundation of Heilongjiang Province Education Department (grant number YJSCX2012-230HLJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.