Zhang Xin, Zhang Yiwen, Tang Hailing, He Jianxing
Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Preventive Medicine Grade 2015, College of Public Hygiene of Guangzhou Medical University, Guangzhou, China.
J Investig Med. 2017 Jan;65(1):72-81. doi: 10.1136/jim-2016-000252. Epub 2016 Sep 23.
Epidermal growth factor receptor (EGFR) gene copy number has been proposed as a candidate biomarker for predicting treatment response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). MEDLINE, PubMed, Cochrane, and Google Scholar databases were searched until October 21, 2015 using the following search terms: lung neoplasms/lung cancer/non-small cell lung cancer/NSCLC, EGFR, gene amplification, copy number, erlotinib, gefitinib, tyrosine-kinase inhibitor/TKI, predictor. 17 studies were included in the analysis with a total of 2047 patients. The overall analysis found that increased EGFR gene copy number was associated with higher overall response rate (ORR), overall survival (OS) and progression-free survival (PFS; p values ≤0.008) compared with patients without a high EGFR gene copy number. Subgroup analysis found that in a population of patients who were primarily Caucasian, a higher EGFR gene copy number was also associated with increased ORR, OS, and PFS (p values ≤0.018). The results were similar in a population of Asian patients, except that a higher EGFR gene copy number was not associated with improved OS (p=0.248). Sensitivity analysis indicated that no one study overly influenced the results and that the findings are robust. The result of the analysis found that EGFR gene copy number was associated with increased OS and PFS, supporting the idea that EGFR gene copy number is a biomarker for response to EGFR-TKI therapy in patients with advanced NSCLC.
表皮生长因子受体（EGFR）基因拷贝数已被提出作为预测晚期非小细胞肺癌（NSCLC）患者对EGFR酪氨酸激酶抑制剂（EGFR-TKIs）治疗反应的候选生物标志物。使用以下检索词在MEDLINE、PubMed、Cochrane和谷歌学术数据库中进行检索，直至2015年10月21日：肺肿瘤/肺癌/非小细胞肺癌/NSCLC、EGFR、基因扩增、拷贝数、厄洛替尼、吉非替尼、酪氨酸激酶抑制剂/TKI、预测指标。分析纳入了17项研究，共2047例患者。总体分析发现，与EGFR基因拷贝数不高的患者相比，EGFR基因拷贝数增加与更高的总缓解率（ORR）、总生存期（OS）和无进展生存期（PFS；p值≤0.008）相关。亚组分析发现，在以白种人为主的患者群体中，较高的EGFR基因拷贝数也与ORR、OS和PFS增加相关（p值≤0.018）。在亚洲患者群体中结果相似，只是较高的EGFR基因拷贝数与OS改善无关（p=0.248）。敏感性分析表明，没有一项研究对结果产生过度影响，研究结果可靠。分析结果发现，EGFR基因拷贝数与OS和PFS增加相关，支持EGFR基因拷贝数是晚期NSCLC患者对EGFR-TKI治疗反应的生物标志物这一观点。
