CAJ | 학술논문

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。揹景與目的近年來，通過對錶皮生長因子受體（epidermal growth factor receptor, EGFR）等相關信號通路的研究及對EGFR酪氨痠激酶抑製劑（EGFR-tyrosine kinase inhibitors, EGFR-TKIs）療效及安全性的探索，證實瞭靶嚮治療已成為肺癌的重要治療手段之一。然而，在各中心試驗中EGFR-TKIs應用于不同EGFR突變亞型患者的效果不儘相同，其原因尚有爭議。因此，本研究通過對比EGFR 19和21外顯子突變肺癌患者的臨床特點和預後分析，以明確不同EGFR突變亞型肺癌患者的臨床病理生理特徵的差異，併為TKIs應用于EGFR不同突變亞型療效差異的研究提供理論依據。方法研究對象為EGFR外顯子19或21突變暘性肺癌患者共113例。其中47例患者採用Real-time PCR或測序分析EGFR突變狀況，餘66例患者則是採用x-TAG液相芯片技術進行分析。收集臨床資料，同時定期隨訪，以死亡作為患者終點事件，併應用SPSS 19.0軟件進行統計學分析。結果在本研究中，EGFR外顯子突變暘性患者共113例。其中，19外顯子突變患者56例，平均年齡為（57.02±11.31）歲；21外顯子突變患者57例，平均年齡為（62.25±7.76）歲，兩組患者在年齡分佈上存在明顯差異（P<0.05）；EGFR外顯子突變暘性患者以女性（61.9%）、非吸煙（72.6%）、腺癌（84.1%）多見，但兩組患者在性彆、吸煙狀況、組織類型、分化程度及TNM分期等臨床特徵方麵均無明顯差異（P>0.05）。進一步分析髮現，19外顯子突變患者相對21外顯子突變患者多好髮于右側（P<0.05）。對所有具有完整隨訪資料的91例（80.53%,91/113）患者預後分析髮現，兩組患者總生存期無統計學差異（中位生存期19外顯子組和21外顯子組分彆為1,051 vs 1,076天，P=0.566）。進一步分析髮現，在年齡>61歲、男性、吸煙、IV期肺癌患者中，19外顯子突變組患者均錶現齣相對較好的預後，但均無統計學差異。結論 EGFR 19外顯子突變肺癌患者相對21外顯子突變肺癌患者年齡較小，且右側原髮較為多見。兩者在性彆、吸煙狀況、組織類型、分期及分化程度上無明顯差彆。兩者總生存時間無差異，但仍然需要進一步研究論證。
배경여목적근년래，통과대표피생장인자수체（epidermal growth factor receptor, EGFR）등상관신호통로적연구급대EGFR락안산격매억제제（EGFR-tyrosine kinase inhibitors, EGFR-TKIs）료효급안전성적탐색，증실료파향치료이성위폐암적중요치료수단지일。연이，재각중심시험중EGFR-TKIs응용우불동EGFR돌변아형환자적효과불진상동，기원인상유쟁의。인차，본연구통과대비EGFR 19화21외현자돌변폐암환자적림상특점화예후분석，이명학불동EGFR돌변아형폐암환자적림상병리생리특정적차이，병위TKIs응용우EGFR불동돌변아형료효차이적연구제공이론의거。방법연구대상위EGFR외현자19혹21돌변양성폐암환자공113례。기중47례환자채용Real-time PCR혹측서분석EGFR돌변상황，여66례환자칙시채용x-TAG액상심편기술진행분석。수집림상자료，동시정기수방，이사망작위환자종점사건，병응용SPSS 19.0연건진행통계학분석。결과재본연구중，EGFR외현자돌변양성환자공113례。기중，19외현자돌변환자56례，평균년령위（57.02±11.31）세；21외현자돌변환자57례，평균년령위（62.25±7.76）세，량조환자재년령분포상존재명현차이（P<0.05）；EGFR외현자돌변양성환자이녀성（61.9%）、비흡연（72.6%）、선암（84.1%）다견，단량조환자재성별、흡연상황、조직류형、분화정도급TNM분기등림상특정방면균무명현차이（P>0.05）。진일보분석발현，19외현자돌변환자상대21외현자돌변환자다호발우우측（P<0.05）。대소유구유완정수방자료적91례（80.53%,91/113）환자예후분석발현，량조환자총생존기무통계학차이（중위생존기19외현자조화21외현자조분별위1,051 vs 1,076천，P=0.566）。진일보분석발현，재년령>61세、남성、흡연、IV기폐암환자중，19외현자돌변조환자균표현출상대교호적예후，단균무통계학차이。결론 EGFR 19외현자돌변폐암환자상대21외현자돌변폐암환자년령교소，차우측원발교위다견。량자재성별、흡연상황、조직류형、분기급분화정도상무명현차별。량자총생존시간무차이，단잉연수요진일보연구론증。
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.