Molecular markers identification of neoadjuvant treatment response in rectal adenocarcinoma patients

• Grant number: 14/06323-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2014
• End date: June 30, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Silvia Regina Rogatto
• Grantee: Luisa Matos Do Canto Alvim
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated scholarship(s): 15/25803-4 - Integrative (genomic, transcriptomic and methylome) analyses of rectal cancer to unravel predictors of neoadjuvant treatment response, BE.EP.DD

Abstract

Colon and rectal tumors are different, not only regarding their location, but also in the type and frequency of genomic and epigenomic alterations. Furthermore, it has been reported different genes and pathways involved in tumors from distinct anatomic location. Colon or rectal tumor resection is recommended in early stages, and in the majority of cases is followed by chemotherapy. However, the treatment options diverge in cases with advanced stages. In rectal carcinomas with stage II-III is recommended neoadjuvant radio- or radiochemotherapy. Interestingly, 25% to 50% of patients with clinical complete response (evaluation of residual tumor) will present pathological complete response, which can be detected only by surgery. Molecular studies on rectal carcinomas have been investigated aiming to detect markers with potential to identify patients that will respond to neoadjuvant treatment. Thus far, the carcinoembryonic antigen (CEA) is the only marker used in the clinic as a prognostic factor after surgery. This study aims to evaluate the methylation and genomic alterations profile, as well as the large-scale transcriptomic analysis in rectal adenocarcinoma biopsies from patients who underwent neoadjuvant therapy. All biopsies were collected prior to chemo/radiotherapy treatment. The integrated analysis of genomic, transcriptomic and methylation data has the potential to highlight drivers that can be used as markers for therapy response and to unveil therapeutic targets for a more efficient treatment of rectal cancer patients. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MATOS DO CANTO, L.; BEGNAMI, M. D.; MARCHI, F.; CATIN, B.; SCAPULATEMPO-NETO, C.; AGUIAR, S., JR.; ROGATTO, S. R.. Gene expression profile reveals a nodal status signature in rectal carcinomas. Annals of Oncology, v. 27, p. 1-pg., 2016-10-01. (14/06323-9)

DO CANTO, LUISA MATOS; LARSEN, SIMON J.; CATIN KUPPER, BRUNA E.; FERREIRA DE SOUZA BEGNAMI, MARIA DIRLEI; SCAPULATEMPO-NETO, CRISTOVAM; PETERSEN, ANNABETH HOGH; AAGAARD, MADS M.; BAUMBACH, JAN; AGUIAR JR, SAMUEL; ROGATTO, SILVIA R.. Increased Levels of Genomic Instability and Mutations in Homologous Recombination Genes in Locally Advanced Rectal Carcinomas. FRONTIERS IN ONCOLOGY, v. 9, MAY 14 2019. (15/25803-4, 08/57887-9, 14/06323-9)

DO CANTO, LUISA MATOS; CURY, SARAH SANTILONI; BARROS-FILHO, MATEUS CAMARGO; CATIN KUPPER, BRUNA ELISA; FERREIRA DE SOUZA BEGNAMI, MARIA DIRLEI; SCAPULATEMPO-NETO, CRISTOVAM; CARVALHO, ROBSON FRANCISCO; MARCHI, FABIO ALBUQUERQUE; OLSEN, DORTE AALUND; MADSEN, JONNA SKOV; et al. Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response. SCIENTIFIC REPORTS, v. 9, JUN 18 2019. (14/06323-9, 15/25803-4, 08/57887-9)

DO CANTO, LUISA MATOS; BARROS-FILHO, MATEUS CAMARGO; RAINHO, CLAUDIA APARECIDA; MARINHO, DIOGO; KUPPER, BRUNA ELISA CATIN; BEGNAMI, MARIA DIRLEI FERREIRA DE SOUZA; SCAPULATEMPO-NETO, CRISTOVAM; HAVELUND, BIRGITTE MAYLAND; LINDEBJERG, JAN; MARCHI, FABIO ALBUQUERQUE; et al. Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer. CANCERS, v. 12, n. 11, NOV 2020. (15/25803-4, 08/57887-9, 14/06323-9)

BELTRAMI, CAROLINE MORAES; DO CANTO, LUISA MATOS; VILLACIS, ROLANDO ANDRE RIOS; PETERSEN, ANNABETH HOGH; AAGAARD, MADS MALIK; CURY, SARAH SANTILONI; FORMIGA, MARIA NIRVANA DA CRUZ; AGUIAR JUNIOR, SAMUEL; ROGATTO, SILVIA REGINA. The repertoire of germline variants in patients with early-onset rectal cancer. CANCER COMMUNICATIONS, v. 42, n. 5, p. 5-pg., 2022-01-14. (15/25803-4, 08/57887-9, 14/06323-9)