TY - JOUR
T1 - Classification of diet-modulated gene signatures at the colon cancer initiation and progression stages
AU - Kachroo, Priyanka
AU - Ivanov, Ivan
AU - Davidson, Laurie A.
AU - Chowdhary, Bhanu P.
AU - Lupton, Joanne R.
AU - Chapkin, Robert S.
N1 - Funding Information:
Acknowledgments We thank Jennifer Goldsby from the Center for Environmental & Rural Health Genomics and Bioinformatics Core for technical assistance. This study was supported by NIH grants CA59034 and CA129444.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Cancer initiation and progression
KW - Chemoprevention
KW - Fish oil
KW - Linear discriminant analysis
UR - http://www.scopus.com/inward/record.url?scp=79958232841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958232841&partnerID=8YFLogxK
U2 - 10.1007/s10620-011-1652-8
DO - 10.1007/s10620-011-1652-8
M3 - Article
C2 - 21409376
AN - SCOPUS:79958232841
SN - 0163-2116
VL - 56
SP - 2595
EP - 2604
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 9
ER -