Cripto-1在食管癌组织中的表达及其与上皮间质转化的关系

Expression of Cripto-1 in esophageal carcinoma and its relationship with epithelial-mesenchymal transformation

目的探讨Cripto-1在食管癌组织中的表达及其与上皮-间质转化(EMT)的关系。方法采用RT-PCR、Western blotting检测41例食管癌患者癌组织、癌旁组织及正常食管黏膜组织中Cripto-1的表达;采用免疫组织化学法检测食管癌组织中Cripto-1及EMT标记物(N-钙黏蛋白、波形蛋白、E-钙黏蛋白)的表达,并结合临床病理资料分析Cripto-1蛋白与N-钙黏蛋白、E-钙黏蛋白、波形蛋白表达的相关性。结果食管癌组织、癌旁组织及正常食管黏膜组织中Cripto-1 mRNA表达水平分别为0.35±0.08、0.22±0.04、0.13±0.03,Cripto-1蛋白表达水平分别为0.62±0.06、0.45±0.07、0.33±0.05,均明显高于癌旁组织及正常食管黏膜组织(P<0.05)。免疫组化染色显示,食管癌组织中Cripto-1、N-钙黏蛋白、波形蛋白、E-钙黏蛋白的阳性表达率分别为53.7%、51.2%、61.0%、36.6%。Cripto-1蛋白表达与N-钙黏蛋白及波形蛋白表达呈正相关(r=0.463,r=0.460,P<0.05),与E-钙黏蛋白表达呈负相关(r=-0.310,P<0.05),与淋巴结转移、远处转移及临床分期显著相关(P<0.05)。结论 Cripto-1在食管癌组织中表达增高,可能与食管癌的发生、发展相关,并可能通过调控EMT促进食管癌的转移。

Objective To investigate the expression of Cripto-1 in esophageal carcinoma and its relationship with epithelial- mesenchymal transformation （EMT）. Methods RT-PCR and Western blotting were used to examine the expression levels of Cripto-1 in carcinoma, paraneoplastic and normal esophageal mucosa tissue of 41 patients with esophageal carcinoma. The protein expressions of Cripto-1 and EMT markers such as N-cadherin, Vimentin and E-cadherin were detected by immunohistochemistry, and the clinical pathologic parameters were simultaneously analyzed. The correlation between Cripto-1 and the expression of N-cadherin, Vimentin and E-cadherin were also analyzed. Results The expression levels of Cripto-1 mRNA and protein were significantly higher in esophageal carcinoma （0.35 ＋ 0.08 and 0.62 ＋ 0.06） than in paraneoplastic （0.22 ＋ 0.04 and 0.45 ＋ 0.07） and normal esophageal mucosa tissue （0.13 ＋ 0.03 and 0.33 ＋ 0.05, P〈0.05）. Immunohistochemistry revealed that the positive expression rates of Cripto-1, N-cadherin, Vimentin and E-cadherin protein in esophageal carcinoma were 53.7%, 51.2%, 61.0% and 36.6% respectively. The expression of Cripto-1 showed a positive correlation with N-cadherin （r=0.463, P〈0.05） and Vimentin （r=0.460, P〈0.05）, while a negative correlation with E-cadherin （r=-0.310, P〈0.05） was found. The expression of Cripto-1 also showed a significant correlation with lymph node metastasis, distant metastasis and clinical stage （P〈0.05）. Conclusion The expression of Cripto-1 is closely related to the carcinogenesis and development of esophageal carcinoma, and may promote the invasion and metastasis of esophageal carcinoma by regulation of EMT.