EGFR mRNA上调在食管鳞状细胞癌患者预后预测中的意义  

Significance of Up-regulation of EGFR m RNA in Prognosis for Esophageal Squamous Cell Carcinoma Patients

作　　者：黄显聪 赵强[1] 凌志强[1] 吴怡晨[1] 刘翔[1] 曹君[1] 韩静[1] 毛伟敏[1] 

机构地区：[1]浙江省肿瘤医院浙江省肿瘤研究所,浙江省胸部肿瘤(肺、食管)诊治技术研究重点实验室,浙江杭州310022

出　　处：《肿瘤学杂志》2016年第3期199-204,共6页Journal of Chinese Oncology

基　　金：国家自然科学基金面上项目(81172081,81572822);浙江省医药卫生科研计划项目(2012KYA029);国家卫生计生委科学研究基金-浙江省医药卫生重大科技计划项目(WKJ-ZJ-1505);浙江省胸部肿瘤(肺、食管)诊治技术研究重点实验室专项基金项目;浙江省卫生高层次创新人才培养工程项目;浙江省新世纪151人才工程重点资助项目

摘　　要：[目的]探讨表皮生长因子受体(EGFR)基因突变和表达在食管鳞状细胞癌中的意义。[方法]分别应用real-time RT-PCR、免疫组化技术检测105例食管鳞状细胞癌组织中EGFR m RNA及蛋白表达水平,应用ADx-ARMS和PCR-Sanger测序法检测上述标本中EGFR基因18、19、20、21外显子突变,分析EGFR表达状态与临床、病理特征及患者生存期的关系。[结果]105例食管鳞状细胞癌组织中仅3例(2.9%,3/105)呈EGFR蛋白弱阳性表达,与癌旁组织相比无显著性差异(P>0.05)。92.4%(97/105)的食管鳞状细胞癌组织中EGFR m RNA表达水平上调,与癌旁组织相比有显著性差异(P=0.000)。且肿瘤组织EGFR m RNA表达水平分别与淋巴结转移(P=0.001)、神经浸润(P=0.039)及TNM分期(P=0.003)显著相关。Kaplan-Meier生存分析显示,EGFR m RNA表达水平上调患者的平均生存期(16.7个月)显著短于EGFR m RNA表达正常/下调患者(19.1个月),其中8个EGFR m RNA正常表达病例生存情况均良好。多因素Cox回归分析表明,EGFR m RNA为食管鳞状细胞癌患者独立的预后因子,其相对危险度为1.368(P<0.001)。[结论]EGFR m RNA可作为食管鳞状细胞癌患者预后标志物,其表达上调提示患者预后不良。[Purpose] To investigate the significance of epidermal growth factor receptor（EGFR）gene mutation and expression in esophageal squamous cell carcinoma（ESCC）. [Methods] Realtime RT-PCR and immunohistochemistry（IHC） technique were used respectively in testing the level of EGFR m RNA and protein expression in 105 cases with ESCC. Exon mutation of18,19,20,21 in EGFR gene in the samples were detected by ADx-ARMS and PCR-Sanger sequencing. The relationship of the status of EGFR expression with clinico pathological parameters and survival in patients with ESCC was analyzed. [Results] Only 3 cases（2.9%,3/105） had weak positive expression of EGFR protein among 105 cases with ESCC,which had no significant difference compared with cancer adjacent tissues（P0.05）. While there was 92.4%（97/105） ESCC tissues with over-expression of EGFR m RNA which had significant difference compared with cancer adjacent tissues（P=0.000）. The expression of EGFR m RNA in ESCC significantly associated with lymph node metastasis（P=0.001）,neural invasion（P=0.039） and TNM stage（P=0.003）. KaplanMeier survival analysis showed that the mean survival of patients with high expression of EGFR m RNA（16.7 months） was significantly shorter than that in patients with normal/low expression（19.1 months）,and 8 cases among the patients with normal expression of EGFR m RNA were still alive. The multivariate Cox regression analysis demonstrated that EGFR m RNA expression was an independent prognostic factor for survival,with RR of 1.368（P 0.001）. [Conclusions] EGFR m RNA might be used as a prognostic marker in patients with ESCC,and its up-regulation indicates poor prognosis for ESCC patients.

关 键 词：食管肿瘤 鳞状细胞癌 表皮生长因子受体 基因突变 基因表达 预后 

分 类 号：R735.1[医药卫生—肿瘤]