EGFR激活突变型非小细胞肺癌HGF/MET异质性表达及其临床意义  

Heterogenous Expression of HGF/MET in Non-small Cell Lung Cancer Harboring EGFR Activating Mutations and Their Clinical Significances

作　　者：张树玲[1] 孙鑫[1] 孙丽[1] 熊志成[1] 孙婧[1] 马洁韬[1] 韩琤波[1] ZHANG Shuling SUN Xin SUN Li XIONG Zhicheng SUN Jing MA Jietao HAN Chengbo(Department of Oncology, Shengjing Hospital, China Medical University, Shenyang 110022, China)

机构地区：[1]中国医科大学附属盛京医院第一肿瘤科,沈阳110022

出　　处：《中国医科大学学报》2016年第10期865-870,876,共7页Journal of China Medical University

基　　金：国家自然科学基金(81372531);辽宁省高等学校杰出青年学者成长计划(F11-262-9-11)

摘　　要：目的分析不同表皮生长因子受体(EGFR)突变状态,外显子19(E19)缺失(del)和外显子21(E21)L858R基因突变蛋白表达与HGF和MET表达的相关性及其与患者预后和生存之间的关系。方法 S-P免疫组化染色法检测55例EGFR突变的非小细胞肺癌(NSCLC)患者切片中E19 del或E21 L858R、MET和HGF 4种蛋白的表达。Kaplan-Meier绘制生存曲线,log-rank比较生存差异。结果 EGFR突变蛋白阳性者HGF和MET蛋白表达阳性率明显高于EGFR突变蛋白阴性者(P<0.05)。HGF表达阴性者与阳性者比较,其总生存期及无病生存期明显延长(P=0.035和P=0.003)。术后复发或晚期使用表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗患者(n=29)中,HGF阴性组较HGF阳性组无疾病进展生存期和总生存期有延长趋势(P=0.19和P=0.10),但差异无统计学意义。结论 HGF可作为EGFR敏感突变NSCLC患者复发和预后生存的判定指标。在EGFR敏感突变的基础上联合HGF指标检测可进一步精确预测EGFR-TKI的疗效和预后生存。Objective To analyze the correlation between the expression of HGF, MET and exon 19 （E19） deletion （de1） and exon 21 （E21） L858R mutations or protein expression, and to explore the relationship between these factors and clinicopathological features and survival in pa- tients harboring activating mutations in the epidermal growth factor receptor （EGFR） gene. Methods The expression of El9 del or E21 L858R, MET and HGF proteins was quantitated by S-P immunohistochemical analysis with specific antibodies in tumor specimens from 55 non-small cell lung cancer （NSCLC） patients who harbored activating EGFR mutations. Kaplan-Meier was adopted to draw the survival curve, and log-rank was used to compare the survival difference. Results Positive expression rates of HGF and MET proteins in patients with EGFR mutation were signifi- cantly higher than those in patients without EGFR mutation （P 〈 0.05 ）. Patients with negative expression of HGF had a significantly increased median disease-free survival （P = 0.003） and overall survival （P = 0.035 ） compared with those with positive expression of HGF. 29 patients with EG- FR mutation who either experienced recurrence after surgery or were initially diagnosed as an advanced disease received epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） therapy in first-line or subsequent lines. Patients with negative expression of HGF had a trend to- wards significance in beth progression-free survival and overall survival compared with those with positive expression of HGF （P = 0.19 and P = 0.10, respectively）. Conclusion HGF might be used as an indicator in patients with non-small cell lung cancer patients harboring activating mutations in EGFR to determine recurrence, prognosis and survival. On the basis of sensitive mutations in EGFR gene, HGF can be used for further accurately prediction of EGFR-TKI efficacy and survival.

关 键 词：非小细胞肺癌 表皮生长因子受体 酪氨酸激酶抑制剂 肝细胞生长因子 MET 激活/敏感突变 

分 类 号：R734.2[医药卫生—肿瘤]