2026-04-13T05:49:17Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1879502025-12-05T09:21:42Zcom_2072_1057col_2072_478798col_2072_478799col_2072_478916col_2072_478917
RECERCAT author Ruiz Bañobre, Juan author Rodriguez Casanova, Aitor author Costa Fraga, Nicolas author Bao Caamano, Aida author Alvarez Castro, Ana author Carreras Presas, Martín author Brozos Vazquez, Elena author Vidal Insua, Yolanda author Vazquez Rivera, Francisca author Candamio Folgar, Sonia author Mosquera Presedo, Manuel author Lago Lestón, Ramón M. author Muinelo Romay, Laura author Vázquez Bueno, José Ángel author Sanz Pamplona, Rebeca author Moreno Aguado, Víctor author Goel, Ajay author Castillo, Lourdes author Martin, Ana C. author Arroyo, Rocio author Esteller, Manel author Crujeiras, Ana B. author López López, Rafael author Díaz Lagares, Angel 2022-07-22T15:38:54Z2022-07-22T15:38:54Z2022-07-092022-07-21T10:24:04Z 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. cc by (c) Ruiz Bañobre, Juan et al., 2022 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Càncer colorectal ADN Metilació Epigenètica Colorectal cancer DNA Methylation Epigenetics Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion