Zhang Hai, Yang Xiaohua, Hu Fang, Li Changhui, Xu Jianlin, Nie Wei, Shen Yinchen, Lou Yuqing, Han Baohui, Zhong Hua, Zhang Xueyan
Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
Onco Targets Ther. 2020 Jun 11;13:5387-5394. doi: 10.2147/OTT.S250024. eCollection 2020.
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.
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.
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).
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.
第一代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）对携带敏感EGFR突变的患者显示出显著的治疗效果，而与耐药相关的机制仍不清楚。本研究旨在阐明Wnt5a表达水平与第一代EGFR-TKIs对携带敏感EGFR突变的肺腺癌患者治疗效果之间的关系。
分析2010年6月1日至2016年12月31日期间我院收治的75例携带敏感EGFR突变并接受第一代EGFR-TKIs治疗的肺腺癌患者的病历。根据第一代EGFR-TKIs的疗效，将患者分为无效组（无进展生存期（PFS）<5个月）和有效组（PFS>26个月）。采用免疫荧光染色、免疫组织化学染色和逆转录聚合酶链反应（RT-PCR）方法检测两组中Wnt5a的表达水平。
75例患者中，36例对第一代EGFR-TKIs敏感（有效组），39例对第一代EGFR-TKIs耐药（无效组）。通过免疫荧光染色检测Wnt5a的定位。免疫组织化学染色显示，无效组中Wnt5a的表达水平显著高于有效组（P=0.0216）。此外，RT-PCR结果显示，无效组中Wnt5a的相对表达水平明显高于有效组（P=0.0135）。
发现Wnt5a的表达水平与第一代EGFR-TKIs对携带敏感EGFR突变的肺腺癌患者的治疗效果相关。
