Context-dependent interpretation of the prognostic value of
BRAF and KRAS mutations in colorectal cancer

J 2013

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

POPOVICI, Vlad, Eva BUDINSKÁ, Fred T BOSMAN, Sabine TEJPAR, Arnaud D ROTH et. al.

Základní údaje

Originální název

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

Autoři

POPOVICI, Vlad (642 Rumunsko, garant, domácí), Eva BUDINSKÁ (703 Slovensko, domácí), Fred T BOSMAN (756 Švýcarsko), Sabine TEJPAR (56 Belgie), Arnaud D ROTH (756 Švýcarsko) a Mauro DELORENZI (756 Švýcarsko)

Vydání

BMC Cancer, LONDON, BIOMED CENTRAL LTD, 2013, 1471-2407

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.319

Kód RIV

RIV/00216224:14110/13:00069862

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1186/1471-2407-13-439

UT WoS

000325080000001

Klíčová slova anglicky

BRAF V600E mutation; Colorectal cancer; KRAS mutations; Stratified analysis; Survival analysis

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 4. 2014 16:12, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

Background: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population.Methods: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05.Results: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation.Conclusions: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it represents a marker of much higher risk than previously considered. KRAS mutation status does not seem to represent a strong prognostic variable.

Citovat

POPOVICI, Vlad, Eva BUDINSKÁ, Fred T BOSMAN, Sabine TEJPAR, Arnaud D ROTH a Mauro DELORENZI. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer. BMC Cancer. LONDON: BIOMED CENTRAL LTD, 2013, roč. 13, č. 439, s. 1-7. ISSN 1471-2407. Dostupné z: https://dx.doi.org/10.1186/1471-2407-13-439.

@article{1126955,
   author = {Popovici, Vlad and Budinská, Eva and Bosman, Fred T and Tejpar, Sabine and Roth, Arnaud D and Delorenzi, Mauro},
   article_location = {LONDON},
   article_number = {439},
   doi = {http://dx.doi.org/10.1186/1471-2407-13-439},
   keywords = {BRAF V600E mutation; Colorectal cancer; KRAS mutations; Stratified analysis; Survival analysis},
   language = {eng},
   issn = {1471-2407},
   journal = {BMC Cancer},
   title = {Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer},
   volume = {13},
   year = {2013}
}

TY  - JOUR
ID  - 1126955
AU  - Popovici, Vlad - Budinská, Eva - Bosman, Fred T - Tejpar, Sabine - Roth, Arnaud D - Delorenzi, Mauro
PY  - 2013
TI  - Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer
JF  - BMC Cancer
VL  - 13
IS  - 439
SP  - 1-7
EP  - 1-7
PB  - BIOMED CENTRAL LTD
SN  - 14712407
KW  - BRAF V600E mutation
KW  - Colorectal cancer
KW  - KRAS mutations
KW  - Stratified analysis
KW  - Survival analysis
N2  - Background: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population.Methods: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05.Results: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation.Conclusions: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it represents a marker of much higher risk than previously considered. KRAS mutation status does not seem to represent a strong prognostic variable.
ER  -

POPOVICI, Vlad, Eva BUDINSKÁ, Fred T BOSMAN, Sabine TEJPAR, Arnaud D ROTH a Mauro DELORENZI. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer. \textit{BMC Cancer}. LONDON: BIOMED CENTRAL LTD, 2013, roč.~13, č.~439, s.~1-7. ISSN~1471-2407. Dostupné z: https://dx.doi.org/10.1186/1471-2407-13-439.

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