Ana B Crujeiras1,2, Sonsoles Morcillo3,4, Angel Diaz-Lagares5, Juan Sandoval6, Daniel Castellano-Castillo3,4, Esperanza Torres7, David Hervas8, Sebastian Moran9, Manel Esteller9,10, Manuel Macias-Gonzalez11,12, Felipe F Casanueva13,3, Francisco J Tinahones3,4. 1. Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela University (USC), Santiago de Compostela, Spain. anabelencrujeiras@hotmail.com. 2. CIBERobn Fisiopatologia de la Nutricion y Obesidad (CB06/03), Madrid, Spain. anabelencrujeiras@hotmail.com. 3. CIBERobn Fisiopatologia de la Nutricion y Obesidad (CB06/03), Madrid, Spain. 4. Unidad de Gestion Clinica Endocrinologia y Nutricion, Instituto de Investigacion Biomédica de Malaga (IBIMA), Complejo Hospitalario de Malaga (Virgen de la Victoria), Universidad de Malaga, Malaga, Spain. 5. Translational Medical Oncology (Oncomet), Instituto de Investigacion Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), CIBERONC, Santiago de Compostela, Spain. 6. Laboratory of Personalized Medicine, Epigenomics Unit, Medical Research Institute La Fe, Valencia, Spain. 7. Unidad de Gestion Clinica de Oncologia Integral. Complejo Hospitalario de Malaga (Virgen de la Victoria), Servicio Andaluz de Salud, Malaga, Spain. 8. Biostatistics Unit, Medical Research Institute La Fe, Valencia, Spain. 9. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain. 10. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 11. CIBERobn Fisiopatologia de la Nutricion y Obesidad (CB06/03), Madrid, Spain. mmacias.mauel@gmail.com. 12. Unidad de Gestion Clinica Endocrinologia y Nutricion, Instituto de Investigacion Biomédica de Malaga (IBIMA), Complejo Hospitalario de Malaga (Virgen de la Victoria), Universidad de Malaga, Malaga, Spain. mmacias.mauel@gmail.com. 13. Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela University (USC), Santiago de Compostela, Spain.
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.
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.
Authors: Francisca Salas-Pérez; Omar Ramos-Lopez; María L Mansego; Fermín I Milagro; José L Santos; José I Riezu-Boj; J Alfredo Martínez Journal: Aging (Albany NY) Date: 2019-03-29 Impact factor: 5.682
Authors: Jihoon E Joo; Mark Clendenning; Ee Ming Wong; Christophe Rosty; Khalid Mahmood; Peter Georgeson; Ingrid M Winship; Susan G Preston; Aung Ko Win; Pierre-Antoine Dugué; Harindra Jayasekara; Dallas English; Finlay A Macrae; John L Hopper; Mark A Jenkins; Roger L Milne; Graham G Giles; Melissa C Southey; Daniel D Buchanan Journal: Cancers (Basel) Date: 2021-05-25 Impact factor: 6.639
Authors: Andrea G Izquierdo; Hatim Boughanem; Angel Diaz-Lagares; Isabel Arranz-Salas; Manel Esteller; Francisco J Tinahones; Felipe F Casanueva; Manuel Macias-Gonzalez; Ana B Crujeiras Journal: Epigenetics Date: 2021-07-26 Impact factor: 4.861
Authors: Ana I Castro; Diego Gomez-Arbelaez; Ana B Crujeiras; Roser Granero; Zaida Aguera; Susana Jimenez-Murcia; Ignacio Sajoux; Patricio Lopez-Jaramillo; Fernando Fernandez-Aranda; Felipe F Casanueva Journal: Nutrients Date: 2018-09-21 Impact factor: 5.717
Authors: Paula M Lorenzo; Andrea G Izquierdo; Angel Diaz-Lagares; Marcos C Carreira; Manuel Macias-Gonzalez; Juan Sandoval; Juan Cueva; Rafael Lopez-Lopez; Felipe F Casanueva; Ana B Crujeiras Journal: Front Endocrinol (Lausanne) Date: 2020-04-23 Impact factor: 5.555
Authors: Hatim Boughanem; Amanda Cabrera-Mulero; Pablo Hernández-Alonso; Mercedes Clemente-Postigo; Felipe F Casanueva; Francisco José Tinahones; Sonsoles Morcillo; Ana B Crujeiras; Manuel Macias-Gonzalez Journal: Clin Epigenetics Date: 2020-06-09 Impact factor: 6.551