Identification of Key Genes for Carcinogenic Pathways Associated With Colorectal Adenoma-To-Carcinoma Progression

Tumour Biol. 2010 Apr;31(2):89-96. doi: 10.1007/s13277-009-0012-1. Epub 2010 Jan 21.

Abstract

Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Aurora Kinase A
  • Aurora Kinases
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Cycle Proteins / analysis
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Humans
  • Immunohistochemistry
  • Protein-Serine-Threonine Kinases / analysis
  • Proto-Oncogene Proteins / analysis
  • Receptor, Platelet-Derived Growth Factor beta / analysis

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Receptor, Platelet-Derived Growth Factor beta
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1