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肺腺癌患者初始治疗前的血清癌胚抗原水平与表皮生长因子受体(EGFR)突变及棘皮动物微管相关蛋白样4(EML4)-间变性淋巴瘤激酶(ALK)融合基因有关。

Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.

作者信息

Wang Wen-Tao, Li Yin, Ma Jie, Chen Xiao-Bing, Qin Jian-Jun

机构信息

Department of Thoracic Surgery, the Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(9):3927-32. doi: 10.7314/apjcp.2014.15.9.3927.

Abstract

BACKGROUND

Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma.

PATIENTS AND METHODS

EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay.

RESULTS

EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation.

CONCLUSIONS

The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

摘要

背景

表皮生长因子受体(EGFR)突变和棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶(EML4-ALK)定义了具有不同临床特征的肺腺癌特定分子亚群。我们的目的是分析EGFR基因突变和EML4-ALK融合基因在肺腺癌中的临床特征及预后价值。

患者与方法

检测了92例中国肺腺癌患者的EGFR基因突变和EML4-ALK融合基因。首次治疗前通过电化学发光免疫分析法测定肿瘤标志物水平。

结果

92例肺腺癌患者中40.2%(37/92)检测到EGFR突变,在从不吸烟者中高频出现(48.3%对比吸烟者中的26.5%;P = 0.040),且在初始治疗前血清癌胚抗原(CEA)水平异常的患者中也高频出现(58.3%对比28.6%,P = 0.004)。多因素分析显示,初始治疗前较高的血清CEA水平与EGFR基因突变独立相关(95%CI:1.476~11.343,P = 0.007)。我们还鉴定出8例携带EML4-ALK融合基因的患者(8.7%,8/92)。与既往报道一致,年龄较轻是这些患者的临床特征(P = 0.008)。7例阳性病例为从不吸烟者,未发现与EGFR突变共存情况。此外,血清CEA浓度低于5 ng/ml的患者中EML4-ALK融合基因的频率似乎高于浓度高于5 ng/ml的患者(P = 0.021)。EML4-ALK阳性组与EML4-ALK阴性组之间或有EGFR突变与无EGFR突变患者之间,在疾病进展时间和总生存期方面未观察到显著差异。

结论

初始治疗前的血清CEA水平可能有助于筛查肺腺癌患者中EGFR突变或EML4-ALK融合基因的存在情况。

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