Integrated exon level expression analysis of driver genes explain their role in colorectal cancer

PLoS One. 2014 Oct 21;9(10):e110134. doi: 10.1371/journal.pone.0110134. eCollection 2014.

Abstract

Integrated analysis of genomic and transcriptomic level changes holds promise for a better understanding of colorectal cancer (CRC) biology. There is a pertinent need to explain the functional effect of genome level changes by integrating the information at the transcript level. Using high resolution cytogenetics array, we had earlier identified driver genes by 'Genomic Identification of Significant Targets In Cancer (GISTIC)' analysis of paired tumour-normal samples from colorectal cancer patients. In this study, we analyze these driver genes at three levels using exon array data--gene, exon and network. Gene level analysis revealed a small subset to experience differential expression. These results were reinforced by carrying out separate differential expression analyses (SAM and LIMMA). ATP8B1 was found to be the novel gene associated with CRC that shows changes at cytogenetic, gene and exon levels. Splice index of 29 exons corresponding to 13 genes was found to be significantly altered in tumour samples. Driver genes were used to construct regulatory networks for tumour and normal groups. There were rearrangements in transcription factor genes suggesting the presence of regulatory switching. The regulatory pattern of AHR gene was found to have the most significant alteration. Our results integrate data with focus on driver genes resulting in highly enriched novel molecules that need further studies to establish their role in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Alternative Splicing
  • Biomarkers / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cytogenetic Analysis
  • Exons
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Principal Component Analysis

Substances

  • Biomarkers
  • Adenosine Triphosphatases
  • ATP8B1 protein, human

Grants and funding

This study was funded by King Abdullah International Medical Research Center through research grant RC10/083 awarded to MAA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.