Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs in Lung Adenocarcinoma Patients with EGFR Gene Mutations
10.3779/j.issn.1009-3419.2014.02.15
- VernacularTitle:Nrf2在EGFR基因突变肺腺癌中的表达及其与EGFR-TKIs疗效间的相关性研究
- Author:
ZHU XIANG
1
;
LIANG LI
;
LIU CHEN
;
YIN WENCHENG
;
CHEN SEN
;
CAO BAOSHAN
Author Information
1. 100191北京，北京大学医学部病理学系，北京大学第三医院病理科
- Keywords:
Lung neoplasms;
EGFR;
EGFR-TKIs;
Nrf2;
Survival time
- From:
Chinese Journal of Lung Cancer
2014;(2):155-162
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have be-come ifrst-line treatment drugs for lung adenocarcinoma patients with EGFR gene mutations. Signiifcant interindividual varia-tions in response rate, progression-free survival (PFS), and overall survival (OS) have been observed. hTe expression level of nuclear factor erythroid-2-related factor 2 (Nrf2) is related to chemoresistance against platinum drugs. Nrf2 overexpression can inhibit the sensitivity of EGFR-TKIs in cells with EGFR-sensitive mutations. hTe aim of this study is to investigate the protein expression level of Nrf2 in lung adenocarcinoma patients with EGFR gene mutations and to elucidate the correlation between Nrf2 expression and response rate of ifrst-line EGFR-TKIs, as well as PFS and OS. Methods Immunohistochemical analysis of Nrf2 in tumor specimens was performed on 31 patients with stage III or IV adenocarcinoma harboring EGFR gene mutations. Results hTe Nrf2-positive rate was 77.4%, whereas Nrf2 nuclear high-expression rate was 38.7%. hTe nuclear expression level of Nrf2 was signiifcantly correlated with response rate (RR) and PFS of EGFR-TKIs (P<0.05), but not with gender, age, smok-ing, differentiation, and OS (P>0.05). hTe Nrf2-positive level was signiifcantly correlated with PFS and OS of EGFR-TKIs (P<0.05), but not with gender, age, smoking, differentiation, EGFR gene mutation status, and RR (P>0.05). hTe PFS and OS of patients with Nrf2-positive expression were signiifcantly shorter than those in patients with negative expression (P<0.05). Furthermore, the nuclear expression level of Nrf2 was the independent predictive factor for EGFR-TKI-induced PFS, and the Nrf2-positive level was the independent predictive factor for EGFR-TKI-induced OS (P<0.05). Conclusion hTe expression level of Nrf2 is signiifcantly correlated with response rate (RR) of EGFR-TKIs, PFS, and OS. hTerefore, Nrf2 may be a useful biomarker in predicting response of EGFR-TKIs in patients with advanced-stage lung adenocarcinoma harboring EGFR gene mutations.
