Epigenome-Wide DNA Methylation Profiling of Normal Mucosa Reveals HLA-F Hypermethylation as a Biomarker Candidate for Serrated Polyposis Syndrome.
Por:
Jung G, Hernández-Illán E, Lozano JJ, Sidorova J, Muñoz J, Okada Y, Quintero E, Hernandez G, Jover R, Carballal S, Cuatrecasas M, Moreno L, Diaz M, Ocaña T, Sánchez A, Rivero L, Ortiz O, Llach J, Castells A, Pellisé M, Goel A, Batlle E and Balaguer F
Publicada:
1 jun 2022
Ahead of Print:
18 abr 2022
Resumen:
Serrated polyposis syndrome (SPS) is associated with a high risk for colorectal cancer. Intense promoter hypermethylation is a frequent molecular finding in the serrated pathway and may be present in normal mucosa, predisposing to the formation of serrated lesions. To identify novel biomarkers for SPS, fresh-frozen samples of normal mucosa from 50 patients with SPS and 19 healthy individuals were analyzed by using the 850K BeadChip Technology (Infinium). Aberrant methylation levels were correlated with gene expression using a next-generation transcriptome profiling tool. Two validation steps were performed on independent cohorts: first, on formalin-fixed, paraffin-embedded tissue of the normal mucosa; and second, on 24 serrated lesions. The most frequently hypermethylated genes were HLA-F, SLFN12, HLA-DMA, and RARRES3; and the most frequently hypomethylated genes were PIWIL1 and ANK3 ( ß = 10%; P < 0.05). In formalin-fixed, paraffin-embedded tissue, we positively validated HLA-F. Expression levels of HLA-F, SLFN12, and HLA-DMA were significantly different between SPS patients and healthy individuals and correlated well with the methylation status of the corresponding differentially methylated region (fold change, >20%; r > 0.55; P < 0.001). Significant hypermethylation of CpGs in the gene body of HLA-F was also found in serrated lesions ( ß = 23%; false discovery rate = 0.01). Epigenome-wide methylation profiling has revealed numerous differentially methylated CpGs in normal mucosa from SPS patients. Significant hypermethylation of the gene body of HLA-F is a novel biomarker candidate for SPS.
Filiaciones:
Jung G:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Hernández-Illán E:
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Lozano JJ:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Bioinformatics Platform, CIBEREHD, Barcelona, Spain
Sidorova J:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Bioinformatics Platform, CIBEREHD, Barcelona, Spain
Muñoz J:
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Okada Y:
Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, Biomedical Research Center, Monrovia, California
Department of Gastroenterology and Oncology, Tokushima University Graduate School, Tokushima, Japan
Quintero E:
Department of Gastroenterology, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain
Hernandez G:
Department of Gastroenterology, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain
:
Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria ISABIAL, Alicante, Spain
Carballal S:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Cuatrecasas M:
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Pathology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Moreno L:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Diaz M:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Ocaña T:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Sánchez A:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Rivero L:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Ortiz O:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Llach J:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Castells A:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Pellisé M:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
Goel A:
Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, Biomedical Research Center, Monrovia, California
City of Hope Comprehensive Cancer Center, Duarte, California
Batlle E:
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
Balaguer F:
Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Faculty of Medicine, University of Barcelona, Barcelona, Spain
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