Comprehensive analysis of DNA methylation and prediction of response to neoadjuvanttherapy in locally advanced rectal cancer

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity Hospital of Southern Denmark-
Autor(es): dc.contributorA.C. Camargo Cancer Center-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorPsykiatrisk Center Sct. Hans-
Autor(es): dc.contributorSírio-Libanês Hospital-
Autor(es): dc.contributorMolecular Oncology Research Center-
Autor(es): dc.contributorDiagnósticos da América (DASA)-
Autor(es): dc.contributorDanish Colorectal Cancer Center South-
Autor(es): dc.contributorTechnical University of Munich-
Autor(es): dc.contributorUniversity of Southern Denmark-
Autor(es): dc.creatorCanto, Luisa Matos Do-
Autor(es): dc.creatorBarros-Filho, Mateus Camargo-
Autor(es): dc.creatorRainho, Cláudia Aparecida [UNESP]-
Autor(es): dc.creatorMarinho, Diogo-
Autor(es): dc.creatorKupper, Bruna Elisa Catin-
Autor(es): dc.creatorBegnami, Maria Dirlei Ferreira de Souza-
Autor(es): dc.creatorScapulatempo-Neto, Cristovam-
Autor(es): dc.creatorHavelund, Birgitte Mayland-
Autor(es): dc.creatorLindebjerg, Jan-
Autor(es): dc.creatorMarchi, Fabio Albuquerque-
Autor(es): dc.creatorBaumbach, Jan-
Autor(es): dc.creatorAguiar, Samuel-
Autor(es): dc.creatorRogatto, Silvia Regina-
Data de aceite: dc.date.accessioned2022-02-22T00:52:19Z-
Data de disponibilização: dc.date.available2022-02-22T00:52:19Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2020-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cancers12113079-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/208068-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/208068-
Descrição: dc.descriptionThe 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.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionUniversidade Estadual Paulista-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionDepartment of Clinical Genetics University Hospital of Southern Denmark-
Descrição: dc.descriptionInternational Research Center–CIPE A.C. Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Head and Neck Surgery Hospital das Clinicas HCFMUSP-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences Sao Paulo State University (Unesp)-
Descrição: dc.descriptionInstitute of Biological Psychiatry Psykiatrisk Center Sct. Hans-
Descrição: dc.descriptionColorectal Cancer Service A.C. Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Pathology Sírio-Libanês Hospital-
Descrição: dc.descriptionMolecular Oncology Research Center-
Descrição: dc.descriptionDiagnósticos da América (DASA)-
Descrição: dc.descriptionDepartment of Oncology University Hospital of Southern Denmark-
Descrição: dc.descriptionDanish Colorectal Cancer Center South-
Descrição: dc.descriptionDepartment of Pathology University Hospital of Southern Denmark-
Descrição: dc.descriptionTUM School of Life Sciences Weihenstephan Technical University of Munich-
Descrição: dc.descriptionInstitute of Regional Health Research Faculty of Health Sciences University of Southern Denmark-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences Sao Paulo State University (Unesp)-
Descrição: dc.descriptionCNPq: #573589/08-9-
Descrição: dc.descriptionUniversidade Estadual Paulista: 001-
Descrição: dc.descriptionCAPES: CAPES-
Formato: dc.format1-19-
Idioma: dc.languageen-
Relação: dc.relationCancers-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject5-fluorouracil-
Palavras-chave: dc.subjectHigh-throughput DNA methylation analysis-
Palavras-chave: dc.subjectPredictive biomarker-
Palavras-chave: dc.subjectTranslational research-
Título: dc.titleComprehensive analysis of DNA methylation and prediction of response to neoadjuvanttherapy in locally advanced rectal cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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