ABSTRACT
Background
Obesity was established as a relevant modifiable risk factor in the onset and progression of colorectal cancer (CRC). This relationship could be mediated by an epigenetic regulation.
Objectives
The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC.
Methods
Fifty-six CRC-diagnosed patients (50 years) were included in the study and categorized according to their body mass index (BMI) as non-obese (BMI ≤ 25 kg/m2) or overweight/obese (BMI > 25 kg/m2). Data from Infinium 450k array-based methylomes of 28 CRC tumor samples were coupled with information on BMI categories. Additionally, DNA methylation results were validated in 28 CRC tumor samples.
Results
The analysis revealed statistically significant differences at 299 CpG sites, and they were mostly characterized as changes towards CpG hypermethylation occurring in the obese group. The 152 identified genes were involved in inflammatory and metabolic functional processes. Among these genes, novel genes were identified as epigenetically regulated in CRC depending on adiposity. ZNF397OS and ZNF543 represented the top scoring associated events that were further validated in an independent cohort and exhibited strong correlation with BMI and excellent and statistically significant efficiency in the discrimination of obese from non-obese CRC patients (area under the curve >0.80; p < 0.05).
Conclusions
The present study identifies a potential epigenome mark of obesity-related CRC that could be useful for precision medicine in the management of this disease taking into account adiposity as a relevant risk factor.
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Acknowledgements
We thank María Amil, Diana García, and Carles Arribas for their technical support, as well as Biobank of the Public Health System of Andalusia (BBSSPA) of the health counseling and the head of the Anatomical Pathology Department of the Hospital Complex of Specialties Virgen de la Victoria Malaga Spain.
Funding
This study was supported by “Centros de Investigacion Biomedica En Red” (CIBERobn) of the “Instituto de Salud Carlos III” (ISCIII), and grants from ISCIII (PI11/01661, PI14/01012, PI15/01114, PE13/00024) co-financed by the European Regional Development Fund (FEDER). DC-C was recipient of an FPU grant from Education Ministry, Madrid, Spain (13/04211). AD-L was funded by the ISCIII through a research contract "Rio Hortega" (CM14/00067) and "Juan Rodés" (JR17/00016), ABC and JS are “Miguel Servet” researchers (ISCIII, CP17/00088 and CP13/00055, respectively) and MM-G was recipient of the Nicolas Monarde program from the Servicio Andaluz de Salud, Junta de Andalucia, Spain (C-0029-2014).
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Crujeiras, A.B., Morcillo, S., Diaz-Lagares, A. et al. Identification of an episignature of human colorectal cancer associated with obesity by genome-wide DNA methylation analysis. Int J Obes 43, 176–188 (2019). https://doi.org/10.1038/s41366-018-0065-6
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DOI: https://doi.org/10.1038/s41366-018-0065-6
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