Base excision repair capacity as a determinant of prognosis and therapy response in colon cancer patients

0495532 - ÚEM 2019 RIV NL eng J - Journal Article
Vodenková, Soňa - Jirásková, Kateřina - Urbanová, Markéta - Kroupa, Michal - Slyšková, Jana - Schneiderová, B. - Levý, M. - Buchler, T. - Liška, V. - Vodičková, Ludmila - Vymetálková, Veronika - Collins, A. - Opattová, Alena - Vodička, Pavel
Base excision repair capacity as a determinant of prognosis and therapy response in colon cancer patients.
Dna Repair. Roč. 72, dec. (2018), s. 77-85. ISSN 1568-7864. E-ISSN 1568-7856
R&D Projects: GA ČR(CZ) GA15-14789S; GA MZd(CZ) NV17-30920A; GA MZd(CZ) NV15-27580A
Institutional support: RVO:68378041
Keywords : colon cancer * base excision repair * microsatellite instability * 5-fluorouracil
OECD category: Gastroenterology and hepatology
Impact factor: 3.711, year: 2018

The DNA-damaging agent 5-fluorouracil represents the most commonly used chemotherapeutic drug for colorectal cancer patients. DNA lesions associated with 5-FU therapy are primarily repaired by base excision repair-BER and mismatch repair-MMR pathways. Published evidence suggests that the individual DNA repair capacity-DRC may affect a patient's prognosis and response to chemotherapy.
The main aim of our study was to investigate BER-DRC in relation to 5-fluorouracil response as potential predictive and/or prognostic biomarker. BER-DRC was supplemented by a microsatellite instability (MSI) analysis which represents an indirect marker of MMR activity in the tumor. All parameters were measured in paired samples of tumor tissue and non-malignant adjacent mucosa of 123 incident colon cancer patients.
Our results indicate that BER-DRC in non-malignant adjacent mucosa was positively associated with overall survival, P = 0.007 and relapse-free survival, P = 0.04. Additionally, in multivariate analysis, good therapy responders in TNM stage II and III with an elevated BER-DRC in mucosa exhibited better overall survival. Moreover, the overall survival of these patients was even better in the presence of a decreased BER-DRC in tumor tissue. The ratio of BER-DRC in tumor tissue over BER-DRC in mucosa positively correlated with advanced tumor stage, P = 0.003. We observed that MSI-high tumors were mostly localized in proximal colon, however, in our cohort, the MSI status affected neither patients prognosis nor survival.
The results of the present study suggest that the level of BER-DRC is associated with patients survival. BER-DRC represents a potential prognostic biomarker, applicable for prediction of therapy response and useful for individual approach to patients.

Permanent Link: http://hdl.handle.net/11104/0294074