组织因子途径抑制物-2和γ-神经突触核蛋白在食管癌中的表达及其与肿瘤细胞浸润、转移和凋亡之间的关系

Expressions of tissue factor pathway inhibitor-2 and synuclein gamma in esophageal cancer and their correlation with local invasion,lymph node metastasis and apoptosis

目的:探讨组织因子途径抑制物-2(tissue factor pathway inhibitor-2,TFPI-2)和γ-神经突触核蛋白(synuclein gamma,SNCG)在食管癌组织中的表达及其与肿瘤浸润、转移和细胞凋亡之间的关系。方法:应用免疫组织化学法检测82例食管癌组织及20例相应癌旁不典型增生组织和54例相应癌旁正常食管组织中TFPI-2、SNCG和基质金属蛋白酶-9(matrix metallo-proteinase-9,MMP-9)的表达,应用TUNEL法检测肿瘤细胞的凋亡并计算细胞凋亡指数(apoptosis index,AI)。结果:TFPI-2和SNCG在食管癌组织、癌旁不典型增生组织及正常食管组织中的阳性表达率分别为30.4%、60.0%、87.0%和63.4%、30.0%、3.7%,3组间两两比较差异均有统计学意义(P<0.01)。TFPI-2和SNCG的表达与肿瘤淋巴结转移、浸润深度、TNM分期和分化程度密切相关(P<0.01),但与患者年龄、性别、肿瘤大小、肿瘤部位和肿瘤大体分型无关(P>0.05)。食管癌组织中TFPI-2与MMP-9的表达呈负相关(r=-0.636,P=0.000),而SNCG与MMP-9的表达呈正相关(r=0.393,P=0.000)。TFPI-2和SNCG的表达与AI有关(P<0.05)。结论:TFPI-2可能通过抑制MMP-9的表达诱导细胞凋亡,抑制食管癌细胞的生长和转移,而SNCG可能在此过程中起着相反的作用,TFPI-2和SNCG有望成为有效的肿瘤标志物和肿瘤基因治疗的新靶点。

Objective：To investigate the expression of tissue factor pathway inhibitor-2（TFPI-2） and synuclein gamma（SNCG） in esophageal cancer and their correlation with local invasion,lymph node metastasis and apoptosis.Methods：The expression of TFPI-2,SNCG,and matrix metalloproteinase-9（MMP-9） was detected by immunohistochemical SP methods in 82 cases of esophageal cancer tissues,20 cases of atypical hyperplasia tissues,and 54 cases of para-cancerous tissues.The apoptosis of esophageal cancer cells was detected by TUNEL staining and apoptosis index（AI） was calculated.Results：The positive rates were 30.4%,60.0%,and 87.0% for TFPI-2 protein and 63.4%,30.0%,and 3.7% for SNCG protein in the tumor tissues,atypical hyperplasia tissues,and tumor-adjacent normal tissues,respectively.There was a significant difference between the three groups（P〈0.01）.The positive expression of TFPI-2 and SNCG correlated with the lymph node metastasis,invasion depth,TNM staging,and differentiation degree of esophageal cancer（P〈0.01）,but did not correlate with age at surgery,gender,tumor location,and pathologic classification（P〉0.05）.The expression of TFPI-2 and MMP-9 was negatively correlated（r=-0.636,P=0.000）.The expression of SNCG and MMP-9 was positively correlated（r=0.393,P=0.000）.AI was related with TFPI-2 and SNCG expression（P〈0.05）.Conclusion：TFPI-2 not only inhibited the expression of MMP-9 but also induces apoptosis of esophageal cancer to prevent tumor invasion and metastasis,however,SNCG plays a contradictory role in cancer development.TFPI-2 and SNCG might serve as new tumor markers and the new targets for tumor gene therapy.