肺腺癌上皮-间质转化相关标识基因检测的临床意义

Detection of epithelial-mesenchymal transition-related genes in lung adenocarcinoma and its significance

目的探讨肺腺癌上皮-间质转化(EMT)相关标识基因钙黏附蛋白E(E-cadherin)、波形蛋白(Vimentin)、Snail和Slug m RNA检测的临床意义。方法收集术后临床病理资料完整的肺腺癌患者117例,抽提肺腺癌组织及相应癌旁组织RNA并逆转录,以GAPDH为内参,利用荧光定量PCR技术检测E-cadherin、Vimentin、Snail和Slug m RNA表达水平,对比癌组织与癌旁组织表达水平,并分析癌组织各基因表达水平与患者性别、年龄、吸烟史、肿块大小、淋巴结转移、病理类型、含微乳头结构(MPP)成分及肿瘤分期的关系。结果与癌旁组织相比,肺腺癌组织E-cadherin m RNA表达水平下调,Vimentin、Snail、Slug m RNA表达水平均上调,差异均有统计学意义(均P<0.05)。有淋巴结转移者癌组织E-cadherin m RNA表达水平下调者所占比例高于无淋巴结转移者,而Vime ntin、Sna il m RNA表达水平上调者所占比例高于无淋巴结转移者(均P<0.05)。浸润性腺癌组Vime ntin m RNA表达水平上调者所占比例高于原位腺癌+微浸润腺癌组(P<0.05)。含MPP成分组癌组织E-cadherin m RNA表达水平下调者所占比例高于不含MPP成分组,而Vime ntin、Sna il、Slug m RNA表达水平上调者所占比例高于不含MPP成分组(均P<0.05)。与I/Ⅱ期肺腺癌组相比,Ⅲ/Ⅳ期肺腺癌组癌组织E-cadherin m RNA表达水平下调者所占比例较高,而Vimentin、Snail、Slug m RNA表达水平上调者所占比例较高(均P<0.05)。结论肺腺癌组织EMT相关标识基因表达水平改变,且与淋巴结转移、病理类型、肿瘤分期相关,提示其可能是评估肺腺癌预后的新指标及肿瘤治疗的新靶点。

Objective To investigate the expression of epithelial mesenchymal transition（EMT）- related genes E- cadherin,Vimentin, Snail and Slug mRNA in lung adenocarcinoma and its significance. Methods One hundred and seventeen patients with lung adenocarcinoma who underwent surgery in Zhoushan Hospital from January 2013 to December 2015 were enrolled. The clinical and pathological data were collected. RNA was extracted and reverse transcripted from lung adenocarcinoma tissue and corresponding adjacent tissues. The expression of E- cadherin, Vimentin, Snail and Slug mRNA was detected by real- time PCR with GAPDH as reference gene. The expression levels were compared between cancer tissues and adjacent tissues; and the relationship of the expression levels of each gene in the cancer tissues with the gender, age, smoking history, tumor size, lymph node metastasis, pathological type, micro papillary component and tumor stage were analyzed. Results Compared with the adjacent tissues, E- cadherin mRNA expression in lung adenocarcinoma tissue was down- regulated, and Vimentin, Snail, Slug mRNA expression was up- regulated （all P〈0.05）. In patients with lymph node metastasis, the proportion of the down- regulated expression of E-cadherin mRNA was higher than that in those without lymph node metastasis （P 〈0.05）. In invasive adenocarcinoma（IA） group, the proportion of the up- regulated expression of Vimentin mRNA was higher than in adenocarcinoma in situ/minimally invasive adenocarcinoma （AIS/MIA） group （P〈0.05）. In micropapillary predominant （MPP） lung adenocarcinoma group, the proportion of the down- regulated expression of E-cadherin mRNA was higher than the group without MPP （all P〈0.05）, while the proportions of the up- regulated expression of Vimentin, Snail, Slug mRNA were higher than the group without MPP （P〈0.05）. Compared with group with grade Ⅰ/Ⅱ, the proportion of the down- regulated expression of E-cadherin mRNA was higher in the group with Ⅲ/Ⅳ, while the proportions of the up- regulated expression of Vimentin, Snail, Slug mRNA was higher （all P〈0.05）. Conclusion The expression levels of EMT- related gene markers in lung adenocarcinoma are changed and they are correlated with lymph node metastasis, pathological type and tumor stage, suggesting that they may be new indicators for evaluating the prognosis of lung adenocarcinoma and potential targets for tumor therapy.