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

Abstract

Hai Zhang,1,* Xiaohua Yang,2,* Fang Hu,1,* Changhui Li,1 Jianlin Xu,1 Wei Nie,1 Yinchen Shen,1 Yuqing Lou,1 Baohui Han,1 Hua Zhong,1 Xueyan Zhang1 1Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 2Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyan Zhang; Hua ZhongDepartment of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of ChinaTel [phone]; [phone]Fax [phone]Email [email protected]; [email protected] 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.Keywords: tyrosine-kinase inhibitors, Wnt5a, epidermal growth factor receptor mutation, therapeutic effect

Keywords

• tyrosine-kinase inhibitors
• wnt5a
• epidermal growth factor receptor mutation
• therapeutic effect