Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas

Clinical Epigenetics

Research

David Gómez-Cabrero¹  María Gallardo-Gómez²  Loretta De Chiara³  Sebastian Moran⁴  Luis Bujanda⁵  Joaquín Cubiella⁶  Rodrigo Jover⁷  Mar Rodríguez-Girondo⁸  Ane Etxart⁹  Antoni Castells^1,10  Francesc Balaguer^1,10  Manel Esteller^1,11  Núria Planell^1,12 

[1] Biological & Environmental Sciences & Engineering Division, King Abdullah University of Science & Technology, Thuwal, Kingdom of Saudi Arabia;Mucosal & Salivary Biology Division, King’s College London Dental Institute, SE1 9RT, London, UK;Translational Bioinformatics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain;CINBIO, Universidade de Vigo, Vigo, Spain;Department of Biochemistry, Genetics and Immunology, CINBIO, Universidade de Vigo, Campus As Lagoas-Marcosende s/n. 36310, Vigo, Spain;Translational Oncology Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain;CINBIO, Universidade de Vigo, Vigo, Spain;Department of Biochemistry, Genetics and Immunology, CINBIO, Universidade de Vigo, Campus As Lagoas-Marcosende s/n. 36310, Vigo, Spain;Translational Oncology Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain;Cancer Genomics Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain;Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de La Granvia, 199. 08908 L’Hospitalet de Llobregat, Barcelona, Spain;Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain;Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Galicia Sur, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Ourense, Spain;Department of Gastroenterology, Hospital General Universitario de Alicante, Alicante, Spain;Servicio de Medicina Digestiva. ISABIAL. Universidad Miguel Hernández, Hospital General Universitario Dr. Balmis, Alicante, Spain;Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands;Department of Surgery, Hospital Universitario Donostia, San Sebastián, Spain;Gastroenterology Department, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain;Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain;Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain;Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain;Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain;Translational Bioinformatics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain;

关键词: Advanced adenomas;    Colorectal cancer;    Cancer prevention;    Circulating cell-free DNA;    DNA methylation;    Liquid biopsy;    Screening;    Serum;   

DOI  :  10.1186/s13148-023-01570-1

 received in 2023-01-20, accepted in 2023-09-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEarly detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC.ResultsFirst, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test.ConclusionsOverall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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