Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/187950
Title: Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
Author: 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
Crujeiras, Ana B.
López López, Rafael
Díaz Lagares, Angel
Keywords: Càncer colorectal
ADN
Metilació
Epigenètica
Colorectal cancer
DNA
Methylation
Epigenetics
Issue Date: 9-Jul-2022
Publisher: Springer Science and Business Media LLC
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s13148-022-01302-x
It is part of: Clinical Epigenetics, 2022, vol. 14, num. 1, p. 86
URI: http://hdl.handle.net/2445/187950
Related resource: https://doi.org/10.1186/s13148-022-01302-x
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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