Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
Clin Lung Cancer. 2014 Jan;15(1):58-66. doi: 10.1016/j.cllc.2013.08.005. Epub 2013 Nov 7.
Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC).
EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis.
High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P = .028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P = .0004). A significant association was shown between EGFR and IGF1R protein overexpression (P < .005). Patients with high expression of both receptors had a poorer overall survival (OS) (P = .04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P = .0004 and P = .0009), with SCC having higher expression levels than ADC.
Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R.
最近的实验和生物标志物证据表明,表皮生长因子受体(EGFR)和胰岛素样生长因子受体 1(IGF1R)在包括肺癌在内的恶性上皮肿瘤的发病机制中相互作用。本研究检查了 EGFR 和 IGF1R 在手术切除的非小细胞肺癌(NSCLC)中的表达及其预后意义。
使用免疫组织化学(IHC)分析评估了 184 例 NSCLC 患者(83 例鳞状细胞癌 [SCC],83 例腺癌 [ADC]和 18 例其他类型)中 EGFR 和 IGF1R 的表达。通过 Western blot 分析检查了来自 40 例 NSCLC 患者(20 例 SCC 和 20 例 ADC)的配对新鲜冷冻正常和肿瘤组织中两种受体的表达。
51%的患者检测到高 EGFR 表达,SCC 的 EGFR 表达高于非 SCC(57.4%比 42.5%;P=.028)。53.8%的患者观察到高 IGF1R 表达,SCC 的表达高于非 SCC(62.6%比 37.3%;P=.0004)。EGFR 和 IGF1R 蛋白过表达之间存在显著相关性(P<.005)。两种受体高表达的患者总生存(OS)较差(P=.04)。与匹配的正常组织相比,切除肿瘤中检测到更高的 EGFR 和 IGF1R 表达(P=.0004 和 P=.0009),SCC 的表达水平高于 ADC。
我们的发现表明 EGFR 和 IGF1R 之间存在密切的相互关系。两种受体的共表达与较差的生存相关。这种亚组患者可能受益于同时针对 EGFR 和 IGF1R 的治疗。