Abstract
Purpose: Amphiregulin (AREG) and epiregulin (EREG) arc ligands of EGFR. Predictive information for anti-EGFR treatment in metastatic colorectal cancer (mCRC) was observed, but data for other agents is limited. Experimental Design: Ligand mRNA expression;RAS, BRAE PIK3CA mutations;and EGFR expression were assessed by qRT-PCR, pyrosequencing, and IHC, respectively, in mCRC tumor tissue of patients participating in the randomized controlled trials FIRE-1, CIOX, and FIRE-3. Normalized mRNA expression was dichotomized using median and third quartile. Overall (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method including univariate and multivariate Cox regression analyses. Penalized spline regression analysis tested interaction of mRNA expression and outcome. Results: Off 688 patients with available material, high AREG expression was detected in 343 (>median) and 172 (>3rd quartile) patients. High AREG expression was associated with significantly higher OS [26.2 vs. 21.5 months, HR = 0.80;95% confidence interval (CI), 0.68-0.94;P = 0.007], PFS (10.0 vs. 8.1 months, HR = 0.74;95% CI, 0.63-0.86;P 0.001), and objective response rate (63.1% vs. 51.6%, P = 0.004) compared to low expression at both threshold values. This effect remained significant in multivariate Cox regression analysis (OS: P = 0.01, PFS: P = 0.002). High AREG mRNA expression interacted significantly with the efficacy of cetuximab compared with bevacizumab (OS: P = 0.02, PFS: P = 0.04) in RAS WT mCRC. Conclusions: High AREG mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-EGFR treatment.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1078-0432 |
Language: | English |
Item ID: | 86851 |
Date Deposited: | 25. Jan 2022, 09:21 |
Last Modified: | 25. Jan 2022, 09:21 |