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Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs.

ABSTRACT: Background and Objective:The first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients harboring sensitive EGFR mutations, while the mechanisms related to drug resistance have still remained elusive. This study aimed to indicate the relationship between the expression level of Wnt5a with therapeutic effects of first-generation EGFR-TKIs on lung adenocarcinoma patients harboring sensitive EGFR mutations. Methods:The medical records of 75 lung adenocarcinoma patients harboring sensitive EGFR mutations, who were admitted to our hospital and received first-generation EGFR-TKIs from June 1, 2010 to December 31, 2016, were analyzed. According to the efficacy of first-generation EGFR-TKIs, patients were divided into ineffective groups (progression-free survival (PFS) <5 months) and effective groups (PFS > 26 months). Immunofluorescence staining, immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) methods were utilized to detect the expression level of Wnt5a in the two groups. Results:Among 75 patients, 36 patients were sensitive to first-generation EGFR-TKIs (effective group) and 39 patients were resistant to first-generation EGFR-TKIs (ineffective group). The location of Wnt5a was detected by immunofluorescence staining. Immunohistochemical staining demonstrated that the expression level of Wnt5a in the ineffective group was significantly higher than that in the effective group (P=0.0216). Besides, results of RT-PCR showed that the relative expression level of Wnt5a was remarkably higher in the ineffective group than that in the effective group (P=0.0135). Conclusion:The expression level of Wnt5a was found to be associated with therapeutic effects of first-generation EGFR-TKIs in lung adenocarcinoma patients harboring sensitive EGFR mutations.

SUBMITTER: Zhang H

PROVIDER: S-EPMC7295535 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs.

Zhang Hai H Yang Xiaohua X Hu Fang F Li Changhui C Xu Jianlin J Nie Wei W Shen Yinchen Y Lou Yuqing Y Han Baohui B Zhong Hua H Zhang Xueyan X

OncoTargets and therapy 20200611

<h4>Background and objective</h4>The first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients harboring sensitive EGFR mutations, while the mechanisms related to drug resistance have still remained elusive. This study aimed to indicate the relationship between the expression level of Wnt5a with therapeutic effects of first-generation EGFR-TKIs on lung adenocarcinoma patients harboring sensitive EGFR mutations. ...[more]

PMID: 32606756

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Project description:BackgroundSeveral randomized controlled trials have suggested that adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were associated with prolonged disease-free survival (DFS) in EGFR-mutated NSCLC patients after radical resection, comparing with chemotherapy or placebo. We aimed to compare the effectiveness of different first-generation EGFR-TKIs as adjuvant treatment in real-world setting.MethodsEarly-stage EGFR mutated NSCLC patients who underwent radical resection and treated with first-generation EGFR-TKIs (gefitinib, erlotinib, icotinib) as adjuvant therapy between Feb 2010 and Jan 2019 were retrieved from a prospectively-maintained database in our center. The primary endpoint was DFS in stage II/III (TNM 8th) patients with exploratory endpoint regarding DFS in stage I patients. Sensitivity analyses were based on propensity score matched (PSM) cohorts. Treatment failure patterns among different TKIs were also compared.ResultsOf 588 eligible patients, 198 patients (33.7%) received gefitinib, 106 patients (17.9%) received erlotinib, and 284 patients (48.2%) received icotinib. The median DFS of stage II/III patients in the gefitinib, erlotinib and icotinib group were 36.1 months (95% CI, 23.9-49.4), 42.8 months (95% CI, 29.6-97.8), and 32.5 months (95% CI, 23.9-49.4), respectively, with no significant difference (log-rank test P=0.22). There was also no significant difference in DFS among stage I patients receiving different TKIs (P=0.12). PSM adjustments and multivariate analyses adjusting for other confounders revealed similar results. In addition, there were no significant differences in treatment failure pattens in different EGFR-TKI arms, especially in terms of brain metastases (6.1% in gefitinb, 7.5% in erlotinib, 3.9% in icotinib) and bone metastases (8.6% in gefitinb, 9.4% in erlotinib, 7.0% in icotinib).ConclusionsThis first and largest real-world study showed that gefitinib, erlotinib, and icotinib demonstrated comparable clinical effectiveness as adjuvant therapy for patients with early-stage EGFR mutated NSCLC.

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Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs.

Publications

Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs.

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