Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs in Lung Adenocarcinoma Patients with EGFR Gene Mutations
Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become first-line treatment drugs for lung adenocarcinoma patients with EGFR gene mutations. Significant interindividual variations in response rate, progression-free survival (PFS), and overall sur...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | zho |
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Chinese Anti-Cancer Association; Chinese Antituberculosis Association
2014-02-01
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| Series: | Chinese Journal of Lung Cancer |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.3779/j.issn.1009-3419.2014.02.15 |
| _version_ | 1818447136443858944 |
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| author | Xiang ZHU Li LIANG Chen LIU Wencheng YIN Sen CHEN Baoshan CAO |
| author_facet | Xiang ZHU Li LIANG Chen LIU Wencheng YIN Sen CHEN Baoshan CAO |
| author_sort | Xiang ZHU |
| collection | DOAJ |
| description | Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become first-line treatment drugs for lung adenocarcinoma patients with EGFR gene mutations. Significant interindividual variations in response rate, progression-free survival (PFS), and overall survival (OS) have been observed. The 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. The 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 first-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 The Nrf2-positive rate was 77.4%, whereas Nrf2 nuclear high-expression rate was 38.7%. The nuclear expression level of Nrf2 was significantly correlated with response rate (RR) and PFS of EGFR-TKIs (P<0.05), but not with gender, age, smoking, differentiation, and OS (P>0.05). The Nrf2-positive level was significantly 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). The PFS and OS of patients with Nrf2-positive expression were significantly 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 The expression level of Nrf2 is significantly correlated with response rate (RR) of EGFR-TKIs, PFS, and OS. Therefore, Nrf2 may be a useful biomarker in predicting response of EGFR-TKIs in patients with advanced-stage lung adenocarcinoma harboring EGFR gene mutations. |
| first_indexed | 2024-12-14T19:58:49Z |
| format | Article |
| id | doaj.art-52610dd6fabd41b689fa7521dcbe7fda |
| institution | Directory Open Access Journal |
| issn | 1009-3419 |
| language | zho |
| last_indexed | 2024-12-14T19:58:49Z |
| publishDate | 2014-02-01 |
| publisher | Chinese Anti-Cancer Association; Chinese Antituberculosis Association |
| record_format | Article |
| series | Chinese Journal of Lung Cancer |
| spelling | doaj.art-52610dd6fabd41b689fa7521dcbe7fda2022-12-21T22:49:13ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34192014-02-0117215516210.3779/j.issn.1009-3419.2014.02.15Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs
in Lung Adenocarcinoma Patients with EGFR Gene MutationsXiang ZHU0Li LIANG1Chen LIU2Wencheng YIN3Sen CHEN4Baoshan CAO5Department of Pathology, Peking University Health Science Center, Third Hospital, Beijing 100191, ChinaDepartment of oncology and radiation sickness, Cancer Center; Peking University Third Hospital, Beijing 100191, ChinaDepartment of Radiology, Peking University Third Hospital, Beijing 100191, ChinaDepartment of oncology and radiation sickness, Cancer Center; Peking University Third Hospital, Beijing 100191, ChinaDepartment of oncology and radiation sickness, Cancer Center; Peking University Third Hospital, Beijing 100191, ChinaDepartment of oncology and radiation sickness, Cancer Center; Peking University Third Hospital, Beijing 100191, ChinaBackground and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become first-line treatment drugs for lung adenocarcinoma patients with EGFR gene mutations. Significant interindividual variations in response rate, progression-free survival (PFS), and overall survival (OS) have been observed. The 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. The 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 first-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 The Nrf2-positive rate was 77.4%, whereas Nrf2 nuclear high-expression rate was 38.7%. The nuclear expression level of Nrf2 was significantly correlated with response rate (RR) and PFS of EGFR-TKIs (P<0.05), but not with gender, age, smoking, differentiation, and OS (P>0.05). The Nrf2-positive level was significantly 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). The PFS and OS of patients with Nrf2-positive expression were significantly 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 The expression level of Nrf2 is significantly correlated with response rate (RR) of EGFR-TKIs, PFS, and OS. Therefore, Nrf2 may be a useful biomarker in predicting response of EGFR-TKIs in patients with advanced-stage lung adenocarcinoma harboring EGFR gene mutations.http://dx.doi.org/10.3779/j.issn.1009-3419.2014.02.15Lung neoplasmsEGFREGFR-TKIsNrf2Survival time |
| spellingShingle | Xiang ZHU Li LIANG Chen LIU Wencheng YIN Sen CHEN Baoshan CAO Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs in Lung Adenocarcinoma Patients with EGFR Gene Mutations Chinese Journal of Lung Cancer Lung neoplasms EGFR EGFR-TKIs Nrf2 Survival time |
| title | Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs
in Lung Adenocarcinoma Patients with EGFR Gene Mutations |
| title_full | Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs
in Lung Adenocarcinoma Patients with EGFR Gene Mutations |
| title_fullStr | Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs
in Lung Adenocarcinoma Patients with EGFR Gene Mutations |
| title_full_unstemmed | Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs
in Lung Adenocarcinoma Patients with EGFR Gene Mutations |
| title_short | Role of the Expression Level of Nrf2 in Predicting Response of EGFR-TKIs
in Lung Adenocarcinoma Patients with EGFR Gene Mutations |
| title_sort | role of the expression level of nrf2 in predicting response of egfr tkis
in lung adenocarcinoma patients with egfr gene mutations |
| topic | Lung neoplasms EGFR EGFR-TKIs Nrf2 Survival time |
| url | http://dx.doi.org/10.3779/j.issn.1009-3419.2014.02.15 |
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