Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity-a pilot study
Cheng Y (1,2), Monteiro C (3,4), Matos A (5,6), You J (1), Fraga A (6,7), Pereira C (3,8), Catalán V (9,10), Rodríguez A (9,10), Gómez-Ambrosi J (9,10), Frühbeck G (9,10,11), Ribeiro R (#3,5,6,12,13), Hu P (#1).
(1) Department of Biochemistry and Medical Genetics & Department of Electrical and Computer Engineering, University of Manitoba, Winnipeg, Canada.
(2) Experimental Center, Northwest University for Nationalities, Lanzhou, People's Republic of China.
(3) Molecular Oncology Group, Portuguese Institute of Oncology, Porto, Portugal.
(4) Research Department, Portuguese League Against Cancer-North, Porto, Portugal.
(5) Laboratory of Genetics and Environmental Health Institute, Faculty of Medicine, University of Lisboa, Lisbon, Portugal.
(6) Tumor & Microenvironment Interactions, i3S/INEB, Institute for Research and Innovation in Health, and Institute of Biomedical Engineering, University of Porto, Porto, Portugal.
(7) Department of Urology, Centro Hospitalar Universitário do Porto, Porto, Portugal.
(8) CINTESIS, Center for Health Technology and Services Research, Faculty of Medicine, e, University of Porto, Porto, Portugal.
(9) Metabolic Research Laboratory, Universidad de Navarra, Pamplona, Spain.
(10) CIBER Fisiopatología de la Obesidad y Nutricion, Instituto de Salud Carlos III, Madrid, Spain.
(11) Department of Endocrinology, Clínica Universidad de Navarra, Pamplona, Spain.
(12) Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
(13) i3S/INEB, Instituto de Investigação e Inovação em Saúde/Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Tumor & Microenvironment Interactions, Rua Alfredo Allen, 208 4200-135 Porto, Portugal.
# Contributed equally
Magazine: Clinical Epigenetics
Date: Apr 17, 2018Endocrinology and Nutrition [SP]
Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients.
DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m-2) and normal weight (NW, BMI < 25 kg m-2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling.
Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples.
Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion.
Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients.
The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.
CITATION Clin Epigenetics. 2018 Apr 17;10:54. doi: 10.1186/s13148-018-0490-3. eCollection 2018
you mayBE INTERESTED
The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.
The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.
Learn why we are different from other healthcare centers. Quality, speed, comfort and results.