Molecular markers identification of neoadjuvant treatment response in rectal adenocarcinoma patients

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)