EGFR 19和21外显子突变肺癌患者的临床特征比较和预后分析

Clinical Characteristics and Outcomes of Lung Cancer Patients with EGFR Mutations in Exons 19 and 21

背景与目的近年来,通过对表皮生长因子受体(epidermal growth factor receptor,EGFR)等相关信号通路的研究及对EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)疗效及安全性的探索,证实了靶向治疗已成为肺癌的重要治疗手段之一。然而,在各中心试验中EGFR-TKIs应用于不同EGFR突变亚型患者的效果不尽相同,其原因尚有争议。因此,本研究通过对比EGFR 19和21外显子突变肺癌患者的临床特点和预后分析,以明确不同EGFR突变亚型肺癌患者的临床病理生理特征的差异,并为TKIs应用于EGFR不同突变亚型疗效差异的研究提供理论依据。方法研究对象为EGFR外显子19或21突变阳性肺癌患者共113例。其中47例患者采用Real-time PCR或测序分析EGFR突变状况,余66例患者则是采用x-TAG液相芯片技术进行分析。收集临床资料,同时定期随访,以死亡作为患者终点事件,并应用SPSS 19.0软件进行统计学分析。结果在本研究中,EGFR外显子突变阳性患者共113例。其中,19外显子突变患者56例,平均年龄为(57.02±11.31)岁;21外显子突变患者57例,平均年龄为(62.25±7.76)岁,两组患者在年龄分布上存在明显差异(P<0.05);EGFR外显子突变阳性患者以女性(61.9%)、非吸烟(72.6%)、腺癌(84.1%)多见,但两组患者在性别、吸烟状况、组织类型、分化程度及TNM分期等临床特征方面均无明显差异(P>0.05)。进一步分析发现,19外显子突变患者相对21外显子突变患者多好发于右侧(P<0.05)。对所有具有完整随访资料的91例(80.53%,91/113)患者预后分析发现,两组患者总生存期无统计学差异(中位生存期19外显子组和21外显子组分别为1,051 vs 1,076天,P=0.566)。进一步分析发现,在年龄>61岁、男性、吸烟、IV期肺癌患者中,19外显子突变组患者均表现出相对较好的预后,但均无统计学差异。结论 EGFR 19外显子突变肺癌患者相对21外显子突变肺癌患者年龄较小,且右侧原发较为多见。两者在性别、吸烟状况、组织类型、分期及分化程度上无明显差别。两者总生存时间无差异,但仍然需要进一步研究论证。

Background and objective 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 signiifcant difference in the effects of EGFR-TKIs, the mechanisms for the difference remain unclear. hTe 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. Methods hTe 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. hTe 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 postopera-tive 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 sotfware. Results EGFR exon mutations 19 and 21 were found in 56 and 57 patients, respectively. hTe 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）. hTe primary tumors of patients with exon 19 mutations were more likely occur in the right lung. hTere were no signiifcant 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. Stratiifcation 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;al-though the differences were not signiifcant. Conclusion Compared to the lung cancer patients with EGFR exon 21 muta-tions, the patients with EGFR exon 19 mutations were younger, and their primary tumors were more likely to occur in the right lung. hTere were no signiifcant 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.