Liu Renwang, Liu Jinghao, Li Xin, Li Ying, Zhao Qingchun, Li Zuosheng, Liu Hongyu, Chen Jun
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, 300052 Tianjin, China.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 300052 Tianjin, China.
Zhongguo Fei Ai Za Zhi. 2014 Nov;17(11):804-11. doi: 10.3779/j.issn.1009-3419.2014.11.06.
Studies on the epidermal growth factor receptor (EGFR) signaling pathways and the therapeutic effects of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have recently proven that targeted therapy has a major role in the treatment of lung cancer. However, the therapeutic effects of EGFR-TKIs on lung cancers with different EGFR mutation subtypes remain unclear. And if there is a significant difference in the effects of EGFR-TKIs, the mechanisms for the difference remain unclear. The aim of this study was to investigate the clinical importance of EGFR mutations in exons 19 and 21 of lung cancer patients and to compare the outcomes of these patients.
The study recruited 113 patients who had non-small cell lung cancer (NSCLC) with EGFR mutations. EGFR mutations were detected for 47 patients using Real-time PCR or DNA sequencinag. The mutations of the remaining patients were determined using xTag-EGFR liquid chip technology. All stages I-III patients underwent radical resection followed by 4 cycles of postoperative chemotherapy. Patients with pleural metastases underwent pleural biopsy, pleurodesis, and chemotherapy only. Patients with distant metastases underwent biopsy and chemotherapy only. Collected clinical data were analyzed using SPSS 19.0 software.
EGFR exon mutations 19 and 21 were found in 56 and 57 patients, respectively. The mean age of patients with exon 19 mutations was lower than the age of the patients with exon 21 mutations (57.02±11.31 years vs 62.25±7.76 years, respectively; P<0.05). The primary tumors of patients with exon 19 mutations were more likely occur in the right lung. There were no significant differences in gender, smoking status, histopathology, level of differentiation, and stage of disease (P>0.05) between the patients with exon 19 and 21 mutations; and survival analysis of 91 (80.5%) patients with complete clinical data found no differences in overall survival. Stratification analysis found out that patients with exon 19 mutations had longer overall survival associated with age>61 years, male gender, ever smoking, and stage IV disease; although the differences were not significant.
Compared to the lung cancer patients with EGFR exon 21 mutations, the patients with EGFR exon 19 mutations were younger, and their primary tumors were more likely to occur in the right lung. There were no significant differences between the lung cancer patients with exon 19 and 21 mutations for overall survival, gender, smoking status, histopathology, level of differentiation, and disease stage.
近期有关表皮生长因子受体（EGFR）信号通路及EGFR酪氨酸激酶抑制剂（EGFR-TKIs）治疗效果的研究证实，靶向治疗在肺癌治疗中发挥着重要作用。然而，EGFR-TKIs对不同EGFR突变亚型肺癌的治疗效果仍不明确。若EGFR-TKIs的疗效存在显著差异，其差异机制也尚不明确。本研究旨在探讨肺癌患者EGFR基因19外显子和21外显子突变的临床意义，并比较这些患者的治疗结果。
本研究纳入了113例患有EGFR突变的非小细胞肺癌（NSCLC）患者。47例患者采用实时荧光定量PCR或DNA测序检测EGFR突变。其余患者的突变情况采用xTag-EGFR液体芯片技术测定。所有I-III期患者均接受根治性切除，术后进行4个周期的化疗。有胸膜转移的患者仅接受胸膜活检、胸膜固定术和化疗。有远处转移的患者仅接受活检和化疗。使用SPSS 19.0软件对收集的临床数据进行分析。
分别在56例和57例患者中发现了EGFR基因19外显子和21外显子突变。19外显子突变患者的平均年龄低于21外显子突变患者（分别为57.02±11.31岁和62.25±7.76岁；P<0.05）。19外显子突变患者的原发肿瘤更易发生于右肺。19外显子和21外显子突变患者在性别、吸烟状况、组织病理学、分化程度和疾病分期方面无显著差异（P>0.05）；对91例（80.5%）有完整临床数据的患者进行生存分析，发现总生存期无差异。分层分析发现，19外显子突变患者在年龄>61岁、男性、曾经吸烟和IV期疾病时总生存期较长；尽管差异不显著。
与EGFR基因21外显子突变的肺癌患者相比，EGFR基因19外显子突变的患者更年轻，其原发肿瘤更易发生于右肺。EGFR基因19外显子和21外显子突变的肺癌患者在总生存期、性别、吸烟状况、组织病理学、分化程度和疾病分期方面无显著差异。
