Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas
Gallardo-Gómez, María (Universidade de Vigo)
Rodríguez-Girondo, Mar (Department of Medical Statistics and Bioinformatics. Leiden University Medical Centre)
Planell, Núria (Universidad Pública de Navarra)
Moran, Sebastián (Institut d'Investigació Biomèdica de Bellvitge)
Bujanda, Luis (Universidad del País Vasco. Instituto de Investigación Sanitaria Biodonostia)
Etxart, Ane (Department of Surgery. Hospital Universitario Donostia)
Castells, Antoni (Universitat de Barcelona)
Balaguer, Francesc (Universitat de Barcelona)
Jover, Rodrigo (Servicio de Medicina Digestiva. Universidad Miguel Hernández)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cubiella, Joaquin (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)
Gómez-Cabrero, David (Mucosal & Salivary Biology Division. King's College London Dental Institute)
De Chiara, Loretta (Galicia Sur Health Research Institute)
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	Background: Early 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. Results: First, 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. Conclusions: Overall, 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.
Ayudas:	Ministerio de Economía y Competitividad PI15/02007 Ministerio de Educación, Cultura y Deporte FPU15/02350
Nota:	We would like to thank Dr. Martínez Zorzano and Professors Rodríguez Berrocal and Páez de la Cadena for their support and scientific advice. We would like to thank Dr. Gómez Zumaquero for the pyrosequencing support. The samples and clinical data of patients included in this study were provided by: the HGUA Biobank (PT13/0010/0044), integrated into the Red Nacional de Biobancos and in the Red Valenciana de Biobancos; SERGAS Biobanco A Coruña ; Basque Biobank/Biodonostia Node; Biobank at the Galicia Sur Health Research Institute; Biobank of Hospital Clínic, Barcelona-IDIBAPS; and CHUS's Biobank (University Hospital Complex of Santiago de Compostela) with the approval of the respective Ethical and Scientific Committees, and have been processed following standard procedures. We acknowledge CESGA (Fundación Pública Galega Centro Tecnolóxico de Supercomputación de Galicia) for providing access to computing facilities to analyze methylation microarray data. All authors have read both the Translational Research's policy on disclosure of potential conflicts of interest and the authorship statement.
Nota:	This work received funding from Plan Nacional I+D+I 2015-2018 (Acción Estratégica en Salud) Instituto de Salud Carlos III (Spain)-FEDER (PI15/02007) and Fundación Científica de la Asociación Española contra el Cáncer (GCB13131592CAST), and support from Centro Singular de Investigación de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) (ED431G/02, Xunta de Galicia and FEDER-European Union). María Gallardo-Gómez was supported by a predoctoral fellowship from Ministerio de Educación, Cultura y Deporte (Spanish Government) (FPU15/02350).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Advanced adenomas ; Colorectal cancer ; Cancer prevention ; Circulating cell‑free DNA ; DNA methylation ; Liquid biopsy ; Screening ; Ser
Publicado en:	Clinical Epigenetics, Vol. 15 Núm. 1 (december 2023) , p. 157, ISSN 1868-7083

DOI: 10.1186/s13148-023-01570-1
PMID: 37794510

17 p, 4.7 MB

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