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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10383611" target="_blank" >RIV/00216208:11110/18:10383611 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/18:00495532 RIV/00216208:11120/18:43917161 RIV/00216208:11140/18:10383611 RIV/00669806:_____/18:10383611 a 2 dalších

Výsledek na webu

<a href="https://doi.org/10.1016/j.dnarep.2018.09.006" target="_blank" >https://doi.org/10.1016/j.dnarep.2018.09.006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.dnarep.2018.09.006" target="_blank" >10.1016/j.dnarep.2018.09.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

The DNA-damaging agent 5-fluorouracil represents the most commonly used chemotherapeutic drug for colorectal cancer patients. DNA lesions associated with 5-fluorouracil 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&apos;s prognosis and response to chemotherapy. With this in mind, we designed a prospective study of which the main aim 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). With respect to MSI, we observed that MSI-high tumors were mostly localized in proximal colon; however, in our cohort, the MSI status affected neither patients&apos; prognosis nor survival. In summary, the results of the present study suggest that the level of BER-DRC is associated with patients&apos; survival. BER-DRC represents a potential prognostic biomarker, applicable for prediction of therapy response and useful for individual approach to patients. Copyright (C) 2018. Published by Elsevier B.V.

Název v anglickém jazyce

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

Popis výsledku anglicky

The DNA-damaging agent 5-fluorouracil represents the most commonly used chemotherapeutic drug for colorectal cancer patients. DNA lesions associated with 5-fluorouracil 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&apos;s prognosis and response to chemotherapy. With this in mind, we designed a prospective study of which the main aim 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). With respect to MSI, we observed that MSI-high tumors were mostly localized in proximal colon; however, in our cohort, the MSI status affected neither patients&apos; prognosis nor survival. In summary, the results of the present study suggest that the level of BER-DRC is associated with patients&apos; survival. BER-DRC represents a potential prognostic biomarker, applicable for prediction of therapy response and useful for individual approach to patients. Copyright (C) 2018. Published by Elsevier B.V.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

DNA Repair

ISSN

1568-7864

e-ISSN

—

Svazek periodika

72

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

77-85

Kód UT WoS článku

000452931200008

EID výsledku v databázi Scopus

2-s2.0-85054467789