An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a
Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer
Patients: Results from Retrospective Analyses of the PETACC-3
Trial

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An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in ...

Přehled o publikaci

J 2020

An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial

STENVANG, Jan; Eva BUDINSKÁ; Eric VAN CUTSEM; Fred BOSMAN; Vlad POPOVICI et. al.

Základní údaje

Originální název

An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial

Autoři

STENVANG, Jan (208 Dánsko); Eva BUDINSKÁ (703 Slovensko, garant, domácí); Eric VAN CUTSEM (56 Belgie); Fred BOSMAN (756 Švýcarsko); Vlad POPOVICI (642 Rumunsko, domácí) a Nils BRUNNER (208 Dánsko)

Vydání

Cancers, BASEL, MDPI, 2020, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14310/20:00116074

Organizace

Přírodovědecká fakulta – Masarykova univerzita – Repozitář

DOI

http://dx.doi.org/10.3390/cancers12040977

UT WoS

000535587400205

EID Scopus

2-s2.0-85083854570

Klíčová slova anglicky

biomarkers; ABCG2; TOP-1; adjuvant irinotecan; colon cancer

Návaznosti

EF17_043/0009632, projekt VaV. LM2018121, projekt VaV. NV19-03-00298, projekt VaV. 857560, interní kód Repo.

Změněno: 25. 1. 2022 14:10, RNDr. Daniel Jakubík

Anotace

V originále

Biomarker-guided treatment for patients with colon cancer is needed. We tested ABCG2 and topoisomerase 1 (TOP1) mRNA expression as predictive biomarkers for irinotecan benefit in the PETACC-3 patient cohort. The present study included 580 patients with mRNA expression data from Stage III colon cancer samples from the PETACC-3 study, which randomized the patients to Fluorouracil/leucovorin (5FUL) +/- irinotecan. The primary end-points were recurrence free survival (RFS) and overall survival (OS). Patients were divided into one group with high ABCG2 expression (above median) and low TOP-1 expression (below 75 percentile) ("resistant") (n = 216) and another group including all other combinations of these two genes ("sensitive") (n = 364). The rationale for the cut-offs were based on the distribution of expression levels in the PETACC-3 Stage II set of patients, where ABCG2 was unimodal and TOP1 was bimodal with a high expression level mode in the top quarter of the patients. Cox proportional hazards regression was used to estimate the hazard ratios and the association between variables and end-points and log-rank tests to assess the statistical significance of differences in survival between groups. Kaplan-Meier estimates of the survival functions were used for visualization and estimation of survival rates at specific time points. Significant differences were found for both RFS (Hazard ratio (HR): 0.63 (0.44-0.92); p = 0.016) and OS (HR: 0.60 (0.39-0.93); p = 0.02) between the two biomarker groups when the patients received FOLFIRI (5FUL+irinotecan). Considering only the Microsatellite Stable (MSS) and Microsatellite Instability-Low (MSI-L) patients (n = 470), the differences were even more pronounced. In contrast, no significant differences were observed between the groups when patients received 5FUL alone. This study shows that the combination of ABCG2 and TOP1 gene expression significantly divided the Stage III colon cancer patients into two groups regarding benefit from adjuvant treatment with FOLFIRI but not 5FUL.

Přiložené soubory

https://is.muni.cz/publication/1672039/1672039.pdf

Citovat

STENVANG, Jan; Eva BUDINSKÁ; Eric VAN CUTSEM; Fred BOSMAN; Vlad POPOVICI a Nils BRUNNER. An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial. Cancers. BASEL: MDPI, 2020, roč. 12, č. 4, s. 1-12. ISSN 2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers12040977.

@article{48166,
   author = {Stenvang, Jan and Budinská, Eva and van Cutsem, Eric and Bosman, Fred and Popovici, Vlad and Brunner, Nils},
   article_location = {BASEL},
   article_number = {4},
   doi = {http://dx.doi.org/10.3390/cancers12040977},
   keywords = {biomarkers; ABCG2; TOP-1; adjuvant irinotecan; colon cancer},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial},
   url = {https://doi.org/10.3390/cancers12040977},
   volume = {12},
   year = {2020}
}

TY  - JOUR
ID  - 48166
AU  - Stenvang, Jan - Budinská, Eva - van Cutsem, Eric - Bosman, Fred - Popovici, Vlad - Brunner, Nils
PY  - 2020
TI  - An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial
JF  - Cancers
VL  - 12
IS  - 4
SP  - 1-12
EP  - 1-12
PB  - MDPI
SN  - 2072-6694
KW  - biomarkers
KW  - ABCG2
KW  - TOP-1
KW  - adjuvant irinotecan
KW  - colon cancer
UR  - https://doi.org/10.3390/cancers12040977
N2  - Biomarker-guided treatment for patients with colon cancer is needed. We tested ABCG2 and topoisomerase 1 (TOP1) mRNA expression as predictive biomarkers for irinotecan benefit in the PETACC-3 patient cohort. The present study included 580 patients with mRNA expression data from Stage III colon cancer samples from the PETACC-3 study, which randomized the patients to Fluorouracil/leucovorin (5FUL) +/- irinotecan. The primary end-points were recurrence free survival (RFS) and overall survival (OS). Patients were divided into one group with high ABCG2 expression (above median) and low TOP-1 expression (below 75 percentile) ("resistant") (n = 216) and another group including all other combinations of these two genes ("sensitive") (n = 364). The rationale for the cut-offs were based on the distribution of expression levels in the PETACC-3 Stage II set of patients, where ABCG2 was unimodal and TOP1 was bimodal with a high expression level mode in the top quarter of the patients. Cox proportional hazards regression was used to estimate the hazard ratios and the association between variables and end-points and log-rank tests to assess the statistical significance of differences in survival between groups. Kaplan-Meier estimates of the survival functions were used for visualization and estimation of survival rates at specific time points. Significant differences were found for both RFS (Hazard ratio (HR): 0.63 (0.44-0.92); p = 0.016) and OS (HR: 0.60 (0.39-0.93); p = 0.02) between the two biomarker groups when the patients received FOLFIRI (5FUL+irinotecan). Considering only the Microsatellite Stable (MSS) and Microsatellite Instability-Low (MSI-L) patients (n = 470), the differences were even more pronounced. In contrast, no significant differences were observed between the groups when patients received 5FUL alone. This study shows that the combination of ABCG2 and TOP1 gene expression significantly divided the Stage III colon cancer patients into two groups regarding benefit from adjuvant treatment with FOLFIRI but not 5FUL.
ER  -

STENVANG, Jan; Eva BUDINSKÁ; Eric VAN CUTSEM; Fred BOSMAN; Vlad POPOVICI a Nils BRUNNER. An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial. \textit{Cancers}. BASEL: MDPI, 2020, roč.~12, č.~4, s.~1-12. ISSN~2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers12040977.