DNA methylome in visceral adipose tissue can discriminate patients with and without colorectal cancer
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
Affiliations
Andrea G Izquierdo
Instituto De Investigacion Sanitaria De Santiago De Compostela (IDIS), Complejo Hospitalario Universitario De Santiago De Compostela (CHUS/SERGAS), and Centro De Investigacion Biomedica En Red Fisiopatologia De La Obesidad Y Nutricion (Ciberobn)
Hatim Boughanem
Virgen De La Victoria University Hospital, University of Malaga (IBIMA), Spain and Centro De Investigacion Biomedica En Red Physiopathology of Obesity and Nutrition (Ciberobn)
Angel Diaz-Lagares
Instituto De Investigacion Sanitaria De Santiago De Compostela (IDIS), Complejo Hospitalario Universitario De Santiago De Compostela (CHUS/SERGAS), and Centro De Investigacion Biomedica En Red Oncología (CIBERONC)
Isabel Arranz-Salas
Virgen de la Victoria University Hospital
Manel Esteller
School of Medicine and Health Sciences, University of Barcelona (UB)
Francisco J Tinahones
Virgen De La Victoria University Hospital, University of Malaga (IBIMA), Spain and Centro De Investigacion Biomedica En Red Physiopathology of Obesity and Nutrition (Ciberobn)
Felipe F Casanueva
Complejo Hospitalario Universitario De Santiago De Compostela (CHUS), Santiago De Compostela University (USC) and Centro De Investigacion Biomedica En Red Fisiopatologia De La Obesidad Y Nutricion (Ciberobn)
Manuel Macias-Gonzalez
Virgen De La Victoria University Hospital, University of Malaga (IBIMA), Spain and Centro De Investigacion Biomedica En Red Physiopathology of Obesity and Nutrition (Ciberobn)
Ana B Crujeiras
Instituto De Investigacion Sanitaria De Santiago De Compostela (IDIS), Complejo Hospitalario Universitario De Santiago De Compostela (CHUS/SERGAS), and Centro De Investigacion Biomedica En Red Fisiopatologia De La Obesidad Y Nutricion (Ciberobn)
Adipose tissue dysfunction, particularly the visceral (VAT) compartment, has been proposed to play a relevant role in colorectal cancer (CRC) development and progression. Epigenetic mechanisms could be involved in this association. The current study aimed to evaluate if specific epigenetic marks in VAT are associated with colorectal cancer (CRC) to identify epigenetic hallmarks of adipose tissue-related CRC. Epigenome-wide DNA methylation was evaluated in VAT from 25 healthy participants and 29 CRC patients, using the Infinium HumanMethylation450K BeadChip. The epigenome-wide methylation analysis identified 170,184 sites able to perfectly separate the CRC and healthy samples. The differentially methylated CpG sites (DMCpGs) showed a global trend for increased methylated levels in CRC with respect to healthy group. Most of the genes encoded by the DMCpGs belonged to metabolic pathways and cell cycle, insulin resistance, and adipocytokine signalling, as well as tumoural transformation processes. In gene-specific analyses, involved genes biologically relevant for the development of CRC include PTPRN2, MAD1L1, TNXB, DIP2C, INPP5A, HDCA4, PRDM16, RPTOR, ATP11A, TBCD, PABPC3, and IER2. The methylation level of some of them showed a discriminatory capacity for detecting CRC higher than 90%, showing IER2 to have the highest capacity. This study reveals that a specific methylation pattern of VAT is associated with CRC. Some of the epigenetic marks identified could provide useful tools for the prediction and personalized treatment of CRC connected to excess adiposity.
