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

Ruiz Bañobre, Juan; Rodriguez Casanova, Aitor; Costa Fraga, Nicolas; Bao Caamano, Aida; Alvarez Castro, Ana; Carreras Presas, Martín; Brozos Vazquez, Elena; Vidal Insua, Yolanda; Vazquez Rivera, Francisca; Candamio Folgar, Sonia; Mosquera Presedo, Manuel; Lago Lestón, Ramón M.; Muinelo Romay, Laura; Vázquez Bueno, José Ángel; Sanz Pamplona, Rebeca; Moreno Aguado, Víctor; Goel, Ajay; Castillo, Lourdes; Martin, Ana C.; Arroyo, Rocio; Esteller, Manel, 1968-; Crujeiras, Ana B.; López López, Rafael; Díaz Lagares, Angel

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

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 eva...

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Autores:	Ruiz Bañobre, Juan, Rodriguez Casanova, Aitor, Costa Fraga, Nicolas, Bao Caamano, Aida, Alvarez Castro, Ana, Carreras Presas, Martín, Brozos Vazquez, Elena, Vidal Insua, Yolanda, Vazquez Rivera, Francisca, Candamio Folgar, Sonia, Mosquera Presedo, Manuel, Lago Lestón, Ramón M., Muinelo Romay, Laura, Vázquez Bueno, José Ángel, Sanz Pamplona, Rebeca, Moreno Aguado, Víctor, Goel, Ajay, Castillo, Lourdes, Martin, Ana C., Arroyo, Rocio, Esteller, Manel, 1968-, Crujeiras, Ana B., López López, Rafael, Díaz Lagares, Angel
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2022
País:	España
Institución:	Universidad de Barcelona
Repositorio:	Dipòsit Digital de la UB
OAI Identifier:	oai:diposit.ub.edu:2445/187950
Acceso en línea:	https://hdl.handle.net/2445/187950
Access Level:	acceso abierto
Palabra clave:	Càncer colorectal ADN Metilació Epigenètica Colorectal cancer DNA Methylation Epigenetics

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spelling	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNARuiz Bañobre, JuanRodriguez Casanova, AitorCosta Fraga, NicolasBao Caamano, AidaAlvarez Castro, AnaCarreras Presas, MartínBrozos Vazquez, ElenaVidal Insua, YolandaVazquez Rivera, FranciscaCandamio Folgar, SoniaMosquera Presedo, ManuelLago Lestón, Ramón M.Muinelo Romay, LauraVázquez Bueno, José ÁngelSanz Pamplona, RebecaMoreno Aguado, VíctorGoel, AjayCastillo, LourdesMartin, Ana C.Arroyo, RocioEsteller, Manel, 1968-Crujeiras, Ana B.López López, RafaelDíaz Lagares, AngelCàncer colorectalADNMetilacióEpigenèticaColorectal cancerDNAMethylationEpigeneticsBackground 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.Springer Science and Business Media LLC2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/187950Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s13148-022-01302-xClinical Epigenetics, 2022, vol. 14, num. 1, p. 86https://doi.org/10.1186/s13148-022-01302-xcc by (c) Ruiz Bañobre, Juan et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1879502026-05-27T06:46:51Z
dc.title.none.fl_str_mv	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
title	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
spellingShingle	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA Ruiz Bañobre, Juan Càncer colorectal ADN Metilació Epigenètica Colorectal cancer DNA Methylation Epigenetics
title_short	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
title_full	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
title_fullStr	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
title_full_unstemmed	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
title_sort	Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
dc.creator.none.fl_str_mv	Ruiz Bañobre, Juan Rodriguez Casanova, Aitor Costa Fraga, Nicolas Bao Caamano, Aida Alvarez Castro, Ana Carreras Presas, Martín Brozos Vazquez, Elena Vidal Insua, Yolanda Vazquez Rivera, Francisca Candamio Folgar, Sonia Mosquera Presedo, Manuel Lago Lestón, Ramón M. Muinelo Romay, Laura Vázquez Bueno, José Ángel Sanz Pamplona, Rebeca Moreno Aguado, Víctor Goel, Ajay Castillo, Lourdes Martin, Ana C. Arroyo, Rocio Esteller, Manel, 1968- Crujeiras, Ana B. López López, Rafael Díaz Lagares, Angel
author	Ruiz Bañobre, Juan
author_facet	Ruiz Bañobre, Juan Rodriguez Casanova, Aitor Costa Fraga, Nicolas Bao Caamano, Aida Alvarez Castro, Ana Carreras Presas, Martín Brozos Vazquez, Elena Vidal Insua, Yolanda Vazquez Rivera, Francisca Candamio Folgar, Sonia Mosquera Presedo, Manuel Lago Lestón, Ramón M. Muinelo Romay, Laura Vázquez Bueno, José Ángel Sanz Pamplona, Rebeca Moreno Aguado, Víctor Goel, Ajay Castillo, Lourdes Martin, Ana C. Arroyo, Rocio Esteller, Manel, 1968- Crujeiras, Ana B. López López, Rafael Díaz Lagares, Angel
author_role	author
author2	Rodriguez Casanova, Aitor Costa Fraga, Nicolas Bao Caamano, Aida Alvarez Castro, Ana Carreras Presas, Martín Brozos Vazquez, Elena Vidal Insua, Yolanda Vazquez Rivera, Francisca Candamio Folgar, Sonia Mosquera Presedo, Manuel Lago Lestón, Ramón M. Muinelo Romay, Laura Vázquez Bueno, José Ángel Sanz Pamplona, Rebeca Moreno Aguado, Víctor Goel, Ajay Castillo, Lourdes Martin, Ana C. Arroyo, Rocio Esteller, Manel, 1968- Crujeiras, Ana B. López López, Rafael Díaz Lagares, Angel
author2_role	author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Càncer colorectal ADN Metilació Epigenètica Colorectal cancer DNA Methylation Epigenetics
topic	Càncer colorectal ADN Metilació Epigenètica Colorectal cancer DNA Methylation Epigenetics
description	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.
publishDate	2022
dc.date.none.fl_str_mv	2022
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/187950
url	https://hdl.handle.net/2445/187950
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1186/s13148-022-01302-x Clinical Epigenetics, 2022, vol. 14, num. 1, p. 86 https://doi.org/10.1186/s13148-022-01302-x
dc.rights.none.fl_str_mv	cc by (c) Ruiz Bañobre, Juan et al., 2022 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by (c) Ruiz Bañobre, Juan et al., 2022 http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Springer Science and Business Media LLC
publisher.none.fl_str_mv	Springer Science and Business Media LLC
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Clíniques) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA

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