title: Classification of diet-modulated gene signatures at the colon cancer initiation and progression stages.
abstract: BACKGROUND
  The effects of dietary polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on intestinal cytokinetics within the context of colon cancer initiation and progression have been extensively studied. n-3 PUFAs have received the most attention due to their potential protective role. However, further investigation of the epigenetic perturbations caused by fatty acids in the context of colon cancer development is needed.
  
  
  METHODS
  We used DNA microarrays to identify discriminative gene signatures (gene combinations) for the purpose of classifying n-3 PUFA-fed, carcinogen-injected, Sprague-Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differing only in the type of fat (corn oil/n-6 PUFA, fish oil/n-3 PUFA, or olive oil/n-9 monounsaturated fatty acid).
  
  
  RESULTS
  The effects of diet on colonic mucosal gene expression signatures during tumor initiation and progression were subsequently compared (12 h and 10 weeks after azoxymethane injection). Microarray analysis revealed that the number of differentially expressed (DE) genes in each of the three diet comparisons increased with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach, we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective (fish oil) diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-performing gene classifiers.
  
  
  CONCLUSIONS
  These results suggest that dietary chemoprotective n-3 PUFA impact genes that regulate the colon stem cell niche and tumor evolution.
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843-4458, USA. PKachroo@cvm.tamu.edu
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kachroo
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivanov
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Davidson
authors.forename: Bhanu P
authors.initials: BP
authors.lastname: Chowdhary
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Lupton
authors.forename: Robert S
authors.initials: RS
authors.lastname: Chapkin
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D003314:Corn Oil / Q000494:pharmacology; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D000069463:Olive Oil; D010938:Plant Oils; D003314:Corn Oil