Zhang Yanwei, Jin Bo, Shao Minhua, Dong Yu, Lou Yuqing, Huang Aimi, Han Baohui
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huai Hai Road, Shanghai, People's Republic of China.
Tumour Biol. 2014 May;35(5):4921-8. doi: 10.1007/s13277-014-1646-1. Epub 2014 Jan 24.
For the detection of epidermal growth factor receptor (EGFR) mutations, tumor tissues may not always be available. Not all the patients harboring EGFR mutation have a clinical response after the treatment of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). EGFR mutations were detected in 70 cases of newly diagnosed non-smoking adenocarcinoma, and patients harboring EGFR mutations received EGFR-TKI treatment. The EGFR mutation status of these patients' blood was analyzed by amplification refractory mutation system (ARMS). The patients' carcinoembryonic antigen (CEA) levels were tested on the third, seventh, 15(th), and 30th days after EGFR-TKI treatment. Forty-four cases were found with EGFR mutations. EGFR mutation rate of CEA high-level group was significantly higher than low-level group (70.8% vs. 40.9%, P = 0.017). Multivariate analysis showed that high-level CEA is independently associated with EGFR gene mutation (P = 0.020, OR = 3.508, 95%CI, 1.223-10.059). The sensitivity of high CEA level and ARMS to predict EGFR mutation were 79.1% and 51.2%. We divided the patients who received EGFR-TKI treatment into three groups by the variation types of CEA. Univariate analysis showed that patients in descending type group have longer progression-free survival (P = 0.001, HR 6.981, 95%CI, 2.534-19.237). Multivariate Cox proportional hazards model analyses shows the same result (P = 0.001, HR 9.82, 95%CI, 3.322-26.031). In conditions of the current technique, using high CEA level to predict EGFR mutations seems to be more sensitive than using EGFR mutations in plasma. The variation types of CEA level could help us to predict the efficacy of EGFR-TKI in patients harboring EGFR mutation within only 1 month of tyrosine kinase inhibitor therapy.
对于表皮生长因子受体（EGFR）突变的检测，肿瘤组织并非总是可获取的。并非所有携带EGFR突变的患者在接受表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗后都有临床反应。在70例新诊断的非吸烟腺癌患者中检测到EGFR突变，携带EGFR突变的患者接受了EGFR-TKI治疗。通过扩增阻滞突变系统（ARMS）分析这些患者血液中的EGFR突变状态。在EGFR-TKI治疗后的第3天、第7天、第15天和第30天检测患者的癌胚抗原（CEA）水平。发现44例存在EGFR突变。CEA高水平组的EGFR突变率显著高于低水平组（70.8%对40.9%，P = 0.017）。多因素分析表明，高水平CEA与EGFR基因突变独立相关（P = 0.020，OR = 3.508，95%CI，1.223 - 10.059）。高CEA水平和ARMS预测EGFR突变的敏感性分别为79.1%和51.2%。我们根据CEA的变化类型将接受EGFR-TKI治疗的患者分为三组。单因素分析表明，下降型组患者的无进展生存期更长（P = 0.001，HR 6.981，95%CI，2.534 - 19.237）。多因素Cox比例风险模型分析显示了相同的结果（P = 0.001，HR 9.82，95%CI，3.322 - 26.031）。在当前技术条件下，使用高CEA水平预测EGFR突变似乎比使用血浆中的EGFR突变更敏感。CEA水平的变化类型可以帮助我们在酪氨酸激酶抑制剂治疗仅1个月内预测EGFR-TKI对携带EGFR突变患者的疗效。
