Přehled o publikaci
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.Basic information
Original name
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
Authors
STENVANG, Jan (208 Denmark); Eva BUDINSKÁ (703 Slovakia, guarantor, belonging to the institution); Eric VAN CUTSEM (56 Belgium); Fred BOSMAN (756 Switzerland); Vlad POPOVICI (642 Romania, belonging to the institution) and Nils BRUNNER (208 Denmark)
Edition
Cancers, BASEL, MDPI, 2020, 2072-6694
Other information
Language
English
Type of outcome
Article in a journal
Country of publisher
Switzerland
Confidentiality degree
is not subject to a state or trade secret
References:
RIV identification code
RIV/00216224:14310/20:00116074
Organization
Přírodovědecká fakulta – Repository – Repository
UT WoS
000535587400205
EID Scopus
2-s2.0-85083854570
Keywords in English
biomarkers; ABCG2; TOP-1; adjuvant irinotecan; colon cancer
Links
EF17_043/0009632, research and development project. LM2018121, research and development project. NV19-03-00298, research and development project. 857560, interní kód Repo.
Changed: 25/1/2022 14:10, RNDr. Daniel Jakubík
Abstract
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.
