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...

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Detalles Bibliográficos
Autores: Cheng, Y. (Yan)|||/items/17f91592-112b-4f6d-8251-fb09d1dca92e, Monteiro, C. (Cátia)|||/items/66830b3f-8ce5-4adb-b982-5528a56b6d85, Matos, A. (Andreia)|||/items/e73d2e40-d96d-4ad5-8374-cfc9f5bae71e, You, J. (Jiaying)|||/items/28d9cd0c-7420-4d18-8ac9-3e634c681bc7, Fraga, A. (Avelino)|||/items/f0c31cc8-d4b8-49ff-b4fd-c0b540c475e3, Pereira, C. (Carina)|||/items/f0b8f462-5a63-4fba-af6f-fcaa489d6d2d, Catalán-Goñi, V. (Victoria)|||/items/9a5a055c-323a-4b41-800f-65abf7f22c79, Rodriguez, A. (Amaia)|||/items/50976a5f-9842-47f1-8a9c-508e59996427, Gomez-Ambrosi, J. (Javier)|||/items/21d09997-940a-45f7-9b4b-0a9f64b2ed8e, Frühbeck, G. (Gema)|||/items/7f0b1f72-bc91-4ab0-a3fd-21e9a3fb663b, Ribeiro, R. (Ricardo)|||/items/95aafc4b-5ad7-423d-bba2-fc4cb0710829, Hu, P. (Pingzhao)|||/items/03ba1c6a-a254-4487-b59c-eb41b17b1dba
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/64841
Acceso en línea:https://hdl.handle.net/10171/64841
Access Level:acceso abierto
Palabra clave:DNA methylation
Periprostatic adipose tissue
Obesity
Prostate cancer
Microenvironment
Descripción
Sumario: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.

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