Selection of adjuvant chemotherapy for colorectal cancer patients based on methylated circulating tumor DNA

Abstract

Colorectal cancer (CRC) is a very importante malignancy, with an global anual rate of about 1.3 million new cases and 5-year survival rate of 50%. The vast majority jof the pacients (85%) can be offered surgery with curative intente, but a consederable part of them will recur with distant metástases. About two thirds of all CRC arise in the colon and after surgery chemotherapy is considered based on final TNM classification. Stage II (T-14 N0 M0) constitutes around 25% of a highly heterogeneous group. The overall prognosis is good with a 5-year overall survival rate of 80-85%, but a small fraction of the patients in stage II has a high mortability comparable to that of stage III and the current literature clearly indicates that adjuvant chemotherapy only methylated in CRC, but not in normal tissue. Methylation of NPY (mNPY) gene was also evaluated in the free circulating DNA from plasma samples and was found methylated in 25 of 50 colorectal cancer patients and in 81 of 88 if patients metastatic disease (92%). In this sense, this proposal aims to evaluate mNPY in the plasma of 100 Danish patients and in a validation cohort of 200 Brazilian patients in order to assess if this would be a suitable biomarker to assist in the prediction of Stage II colon cancer patients who will benefit from adjuvant therapy. Also, a plasma biorepository will be collected aiming the evaluation of further promising biomarkers. (AU)