宫颈鳞癌中EZH2的表达与自噬的关系及其预后价值

Relationship between EZH2 expression and autophagy and its prognostic value in cervical squamous cell carcinoma

目的探究宫颈鳞癌中zeste增强子同源物2(inhancer of zeste homolog 2,EZH2)的表达与自噬的关系及其预后价值。方法选取80例宫颈鳞癌、30例宫颈上皮内瘤变(CIN)Ⅱ—Ⅲ、30例CINⅠ和30例慢性宫颈炎患者为研究对象。采用免疫组织化学方法检测EZH2、自噬相关蛋白Beclin-1和微管相关蛋白1轻链3(LC3)蛋白在各组宫颈组织中的表达情况;分析三者与宫颈鳞癌患者各临床病理参数的相关性。对宫颈鳞癌患者进行随访,采用Cox比例风险回归模型分析EZH2、Beclin-1和LC3蛋白表达水平与患者预后的关系。结果EZH2蛋白在宫颈鳞癌、宫颈上皮内瘤变(CIN)Ⅱ—Ⅲ、CINⅠ和慢性宫颈炎组织中的阳性表达率分别为78.8%、60.0%、33.3%和10.0%(P<0.05),Beclin-1蛋白的阳性表达率分别为27.5%、70.0%、76.7%和86.7%(P<0.05),LC3蛋白的阳性表达率分别为30.0%、70.0%、73.3%和80.0%(P<0.05)。EZH2蛋白表达水平与宫颈鳞癌国际妇产科协会(FIGO)分期、分化程度、肿瘤大小及淋巴结转移显著相关(P<0.05),与患者年龄无相关性(P>0.05);Beclin-1、LC3与FIGO分期、淋巴结转移显著相关(P<0.05),与年龄、分化程度、肿瘤大小无关(P>0.05)。相关分析显示EZH2与Beclin-1、LC3的蛋白表达水平均呈负相关(r=-0.296,P<0.01;r=-0.327,P<0.01);Beclin-1与LC3的蛋白表达水平呈正相关(r=0.391,P<0.01)。多因素Cox回归分析显示,EZH2、Beclin-1和LC3是宫颈鳞癌患者预后的独立危险因素。结论宫颈鳞癌组织中高表达的EZH2可能通过抑制细胞自噬参与宫颈鳞癌的发生、发展,从而影响宫颈癌患者的预后。

Objective To investigate the relationship between inhancer of zeste homolog 2(EZH2)expression and autophagy and its prognostic value in cervical squamous cell carcinoma.MethodsA total of 80 patients with cervical squamous cell carcinoma,30 patients with cervical intraepithelial neoplasia(CIN)Ⅱ-Ⅲ,30 patients with CINⅠ,and 30 patients with chronic cervicitis were selected.Immunohistochemistry was used to detect the expression of EZH2,autophagy associated proteins Beclin-1 and microtubule-associated protein 1 light chain 3(LC3)proteins in the cervical tissues of each group.The correlation between the three factors and the clinicopathological parameters of cervical squamous cell carcinoma was analyzed.Patients with cervical squamous cell carcinoma were followed up,and the Cox proportional hazard regression model was used to analyze the relationship between the protein expression levels of EZH2,Beclin-1 and LC3 and the survival of patients.ResultsThe positive expression rates of EZH2 protein in cervical squamous cell carcinoma,CINⅡ-Ⅲ,CINⅠand chronic cervicitis tissues were 78.8%,60.0%,33.3%and 10.0%,respectively(P<0.05),the positive expression rates of Beclin-1 protein were 27.5%,70.0%,76.7%and 86.7%,respectively(P<0.05),and the positive expression rates of LC3 protein were 30.0%,70.0%,73.3%and 80.0%,respectively(P<0.05).The expression level of EZH2 protein was significantly correlated with FIGO stage,differentiation degree,tumor size and lymph node metastasis of cervical squamous cell carcinoma(P<0.05),but not correlated with age(P>0.05).Beclin-1 and LC3 were significantly correlated with FIGO(International Federation of Gynecology and Obstetrics)stage and lymph node metastasis(P<0.05),but not with age,tissue differentiation degree,and tumor size(P>0.05).Correlation analysis showed that the protein expression levels of EZH2 were negatively correlated with Beclin-1and LC3(r=-0.296,P<0.01;r=-0.327,P<0.01),while Beclin-1 was positively correlated with LC3 protein(r=0.391,P<0.01).Multivariate Cox regression analysis showed that EZH2,Beclin-1 and LC3 were independent risk factors for the prognosis of cervical squamous cell carcinoma patients.ConclusionsThe high expression of EZH2 in cervical squamous cell carcinoma tissues may be involved in the occurrence and development of cervical squamous cell carcinoma through inhibiting autophagy,thus affecting the prognosis of cervical cancer patients.