Brasil | Artículos de revistas
dc.contributorUniversity Hospital of Southern Denmark
dc.contributorA.C. Camargo Cancer Center
dc.contributorUniversidade de São Paulo (USP)
dc.contributorUniversidade Estadual Paulista (Unesp)
dc.contributorPsykiatrisk Center Sct. Hans
dc.contributorSírio-Libanês Hospital
dc.contributorMolecular Oncology Research Center
dc.contributorDiagnósticos da América (DASA)
dc.contributorDanish Colorectal Cancer Center South
dc.contributorTechnical University of Munich
dc.contributorUniversity of Southern Denmark
dc.date.accessioned2021-06-25T11:05:48Z
dc.date.accessioned2022-12-19T22:36:35Z
dc.date.available2021-06-25T11:05:48Z
dc.date.available2022-12-19T22:36:35Z
dc.date.created2021-06-25T11:05:48Z
dc.date.issued2020-11-01
dc.identifierCancers, v. 12, n. 11, p. 1-19, 2020.
dc.identifier2072-6694
dc.identifierhttp://hdl.handle.net/11449/208068
dc.identifier10.3390/cancers12113079
dc.identifier2-s2.0-85093914700
dc.identifier8814823545159504
dc.identifier0000-0002-0285-1162
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/5388665
dc.description.abstractThe treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs. External validation was carried out with The Cancer Genome Atlas-Rectal Adenocarcinoma (TCGA-READ 99 cases). A classifier based on three-CpGs DM (linked to OBSL1, GPR1, and INSIG1 genes) was able to discriminate pCR from incomplete responders with high sensitivity and specificity. The methylation levels of the selected CpGs confirmed the predictive value of our classifier in 77 LARCs evaluated by bisulfite pyrosequencing. Evaluation of external datasets (TCGA-READ, GSE81006, GSE75546, and GSE39958) reproduced our results. As the three CpGs were mapped near to regulatory elements, we performed an integrative analysis in regions associated with predicted cisregulatory elements. A positive and inverse correlation between DNA methylation and gene expression was found in two CpGs. We propose a novel predictive tool based on three CpGs potentially useful for pretreatment screening of LARC patients and guide the selection of treatment modality.
dc.languageeng
dc.relationCancers
dc.sourceScopus
dc.subject5-fluorouracil
dc.subjectHigh-throughput DNA methylation analysis
dc.subjectPredictive biomarker
dc.subjectTranslational research
dc.titleComprehensive analysis of DNA methylation and prediction of response to neoadjuvanttherapy in locally advanced rectal cancer
dc.typeArtículos de revistas


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