Digestive Diseases and Sciences

, Volume 56, Issue 9, pp 2595–2604

Classification of Diet-Modulated Gene Signatures at the Colon Cancer Initiation and Progression Stages

  • Priyanka Kachroo
  • Ivan Ivanov
  • Laurie A. Davidson
  • Bhanu P. Chowdhary
  • Joanne R. Lupton
  • Robert S. Chapkin
Original Article

DOI: 10.1007/s10620-011-1652-8

Cite this article as:
Kachroo, P., Ivanov, I., Davidson, L.A. et al. Dig Dis Sci (2011) 56: 2595. doi:10.1007/s10620-011-1652-8

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.

Keywords

Chemoprevention Cancer initiation and progression Fish oil Linear discriminant analysis 

Abbreviations

AOM

Azoxymethane

DE

Differentially expressed

LDA

Linear discriminant analysis

MUFA

Monounsaturated fatty acids

PUFA

Polyunsaturated fatty acids

Supplementary material

10620_2011_1652_MOESM1_ESM.pdf (275 kb)
Supplementary material 1 (PDF 274 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Priyanka Kachroo
    • 1
  • Ivan Ivanov
    • 2
  • Laurie A. Davidson
    • 3
  • Bhanu P. Chowdhary
    • 1
  • Joanne R. Lupton
    • 3
  • Robert S. Chapkin
    • 3
  1. 1.Department of Veterinary Integrative BiosciencesTexas A&M UniversityCollege StationUSA
  2. 2.Department of Veterinary Physiology and PharmacologyTexas A&M UniversityCollege StationUSA
  3. 3.Program in Integrative Nutrition and Complex DiseasesKleberg Center, Center for Environmental and Rural Health, Texas A&M UniversityCollege StationUSA

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