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Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study
BACKGROUND: 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 ob...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904983/ https://www.ncbi.nlm.nih.gov/pubmed/29692867 http://dx.doi.org/10.1186/s13148-018-0490-3 |
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author | Cheng, Yan Monteiro, Cátia Matos, Andreia You, Jiaying Fraga, Avelino Pereira, Carina Catalán, Victoria Rodríguez, Amaia Gómez-Ambrosi, Javier Frühbeck, Gema Ribeiro, Ricardo Hu, Pingzhao |
author_facet | Cheng, Yan Monteiro, Cátia Matos, Andreia You, Jiaying Fraga, Avelino Pereira, Carina Catalán, Victoria Rodríguez, Amaia Gómez-Ambrosi, Javier Frühbeck, Gema Ribeiro, Ricardo Hu, Pingzhao |
author_sort | Cheng, Yan |
collection | PubMed |
description | BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-018-0490-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5904983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59049832018-04-24 Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study Cheng, Yan Monteiro, Cátia Matos, Andreia You, Jiaying Fraga, Avelino Pereira, Carina Catalán, Victoria Rodríguez, Amaia Gómez-Ambrosi, Javier Frühbeck, Gema Ribeiro, Ricardo Hu, Pingzhao Clin Epigenetics Research BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-018-0490-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-17 /pmc/articles/PMC5904983/ /pubmed/29692867 http://dx.doi.org/10.1186/s13148-018-0490-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Cheng, Yan Monteiro, Cátia Matos, Andreia You, Jiaying Fraga, Avelino Pereira, Carina Catalán, Victoria Rodríguez, Amaia Gómez-Ambrosi, Javier Frühbeck, Gema Ribeiro, Ricardo Hu, Pingzhao Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
title | Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
title_full | Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
title_fullStr | Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
title_full_unstemmed | Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
title_short | Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
title_sort | epigenome-wide dna methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904983/ https://www.ncbi.nlm.nih.gov/pubmed/29692867 http://dx.doi.org/10.1186/s13148-018-0490-3 |
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