Autor(es):
Canto, Luisa Matos Do ; Barros-Filho, Mateus Camargo ; Rainho, Cláudia Aparecida [UNESP] ; Marinho, Diogo ; Kupper, Bruna Elisa Catin ; Begnami, Maria Dirlei Ferreira de Souza ; Scapulatempo-Neto, Cristovam ; Havelund, Birgitte Mayland ; Lindebjerg, Jan ; Marchi, Fabio Albuquerque ; Baumbach, Jan ; Aguiar, Samuel ; Rogatto, Silvia Regina
Data: 2021
Identificador Persistente: http://hdl.handle.net/11449/208068
Origem: Oasisbr
Assunto(s): 5-fluorouracil; High-throughput DNA methylation analysis; Predictive biomarker; Translational research
Descrição
Made available in DSpace on 2021-06-25T11:05:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Universidade Estadual Paulista
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
The 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.
Department of Clinical Genetics University Hospital of Southern Denmark
International Research Center–CIPE A.C. Camargo Cancer Center
Department of Head and Neck Surgery Hospital das Clinicas HCFMUSP
Department of Chemical and Biological Sciences Institute of Biosciences Sao Paulo State University (Unesp)
Institute of Biological Psychiatry Psykiatrisk Center Sct. Hans
Colorectal Cancer Service A.C. Camargo Cancer Center
Department of Pathology Sírio-Libanês Hospital
Molecular Oncology Research Center
Diagnósticos da América (DASA)
Department of Oncology University Hospital of Southern Denmark
Danish Colorectal Cancer Center South
Department of Pathology University Hospital of Southern Denmark
TUM School of Life Sciences Weihenstephan Technical University of Munich
Institute of Regional Health Research Faculty of Health Sciences University of Southern Denmark
Department of Chemical and Biological Sciences Institute of Biosciences Sao Paulo State University (Unesp)
CNPq: #573589/08-9
Universidade Estadual Paulista: 001
CAPES: CAPES
