Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA.

Autor: Ruiz-Bañobre J; Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain., Rodriguez-Casanova A; Cancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Roche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), 15706, Santiago de Compostela, Spain.; Universidade de Santiago de Compostela (USC), 15782, Santiago de Compostela, Spain., Costa-Fraga N; Cancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Universidade de Santiago de Compostela (USC), 15782, Santiago de Compostela, Spain., Bao-Caamano A; Cancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Universidade de Santiago de Compostela (USC), 15782, Santiago de Compostela, Spain., Alvarez-Castro A; Department of Gastroenterology and Hepatology, University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain., Carreras-Presas M; Department of Gastroenterology and Hepatology, University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain., Brozos-Vazquez E; Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain., Vidal-Insua Y; Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain., Vazquez-Rivera F; Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain., Candamio-Folgar S; Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain., Mosquera-Presedo M; Cancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Universidade de Santiago de Compostela (USC), 15782, Santiago de Compostela, Spain., Lago-Lestón RM; Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain., Muinelo-Romay L; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain.; Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain., Vázquez-Bueno JÁ; Department of Pathology, Complejo Hospitalario Universitario de Ferrol (SERGAS), 15405, Ferrol, Spain., Sanz-Pamplona R; Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), 08907, Barcelona, Spain.; Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), 08907, Barcelona, Spain.; Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain., Moreno V; Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), 08907, Barcelona, Spain.; Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), 08907, Barcelona, Spain.; Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain.; Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08907, Barcelona, Spain., Goel A; Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott and White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.; Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA, USA.; City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Castillo L; Advanced Marker Discovery (AMADIX), 47004, Valladolid, Spain., Martin AC; Advanced Marker Discovery (AMADIX), 47004, Valladolid, Spain., Arroyo R; Advanced Marker Discovery (AMADIX), 47004, Valladolid, Spain., Esteller M; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain.; Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain.; Institucio Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain.; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain., Crujeiras AB; Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.; Centro de Investigación Biomédica en Red Fisiopatología de La Obesidad y Nutrición (CIBERobn), ISCIII, 28029, Madrid, Spain., López-López R; Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain. rafael.lopez.lopez@sergas.es.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain. rafael.lopez.lopez@sergas.es.; Roche-Chus Joint Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), 15706, Santiago de Compostela, Spain. rafael.lopez.lopez@sergas.es., Díaz-Lagares A; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain. angel.diaz.lagares@sergas.es.; Cancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain. angel.diaz.lagares@sergas.es.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2022 Jul 09; Vol. 14 (1), pp. 86. Date of Electronic Publication: 2022 Jul 09.
DOI: 10.1186/s13148-022-01302-x
Abstrakt: Background: Current noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions.
Methods: We evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR.
Results: LINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients.
Conclusions: Hypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions.
(© 2022. The Author(s).)
Databáze: MEDLINE
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