Clinicopathological features and epidermal growth factor receptor mutations associated with epithelial-mesenchymal transition in non-small cell lung cancer
Clinicopathological features and epidermal growth factor receptor mutations associated with epithelial-mesenchymal transition in non-small cell lung cancer
复制标题
非小细胞肺癌的临床病理特征及与上皮间质转化相关的表皮生长因子受体突变
DOI：
10.1111/j.1440-1843.2009.01496.x
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发表时间：
2009-04-01
期刊：
影响因子：
6.9
通讯作者：
Su, Chun-Xia
中科院分区：
文献类型：
--
作者：
Deng, Qin-Fang;Zhou, Cai-Cun;Su, Chun-Xia
表皮生长因子受体（EGFR）的小分子抑制剂已在非小细胞肺癌（NSCLC）患者中进行了广泛研究。发现分子生物标志物，以确定受益于EGFR酪氨酸激酶抑制剂（TKI）的NSCLC患者的亚组已成为一个重要的研究领域。最近的研究表明，肿瘤中的上皮-间质转化（EMT）降低了EGFR信号通路的细胞需求，这可能提供一个分子特征，以确定最有可能对靶向EGFR TKI治疗产生应答的NSCLC患者。本研究探讨了非小细胞肺癌的临床病理特征和与EMT相关的EGFR突变，并对62例非小细胞肺癌手术切除标本进行了免疫组化染色检测EMT状态。计算肿瘤上皮表型的频率，并通过逻辑回归确定与临床病理特征和EGFR基因型的关联强度，上皮表型的总频率为35.48%（22/62）。基于单变量分析，EGFR突变体的上皮表型（E-钙粘蛋白阳性）频率高于野生型（77.78% vs 18.18%; P < 0.0001），女性高于男性（54.55% vs 25%; P = 0.02）。多因素Logistic回归分析显示，只有EGFR基因型（OR = 0.063，95%CI：0.013-0.3，P = 0.0005）与上皮细胞表型有显著相关性，在NSCLC患者中，EGFR突变患者的上皮细胞标志物频率更高。
Small molecular inhibitors of the epidermal growth factor receptor (EGFR) have been extensively studied in non-small cell lung cancer (NSCLC) patients. The discovery of molecular biomarkers that identify the subgroups of NSCLC patients benefiting from EGFR tyrosine kinase inhibitor (TKI) has become an important area of investigation. Recent studies have suggested that epithelial-mesenchymal transition (EMT) in tumours decreases the cellular requirements for EGFR signalling pathway, and this may provide a molecular signature to define those NSCLC patients most likely to respond to treatment with targeted EGFR TKI. This research explored the clinicopathological features and EGFR mutations associated with EMT in NSCLC.The EMT status in surgically resected specimens from 62 patients with NSCLC was tested by immunohistochemical staining. The frequency of tumour epithelial phenotype was calculated and the strength of the association with clinicopathological features and EGFR genotype was determined by logistic regression.The overall frequency of the epithelial phenotype was 35.48% (22 of 62). Based on univariate analyses, the frequency of the epithelial phenotype (E-cadherin-positive) was greater for EGFR mutants versus wild types (77.78% vs 18.18%; P < 0.0001) and women versus men (54.55% vs 25%; P = 0.02). Multivariate logistic analysis showed that only the EGFR genotype (odds ratio, 0.063; 95% CI: 0.013-0.3; P = 0.0005) was significantly associated with the epithelial phenotype.In patients with NSCLC, there is a higher frequency of epithelial markers in patients with EGFR mutation.