乳腺癌组织中ZEB2、E-Cad表达与患者预后的关系

Relations of ZEB2 and E-Cad expressions in breast cancer tissues with prognosis

目的 探讨E盒结合锌指蛋白2(ZEB2)和上皮型钙黏蛋白(E-Cad)在乳腺癌组织中的表达及其在患者预后评估中的价值。方法 收集80例乳腺癌患者的癌组织样本及对应的癌旁组织(距癌组织≤3 cm)样本。采用免疫组化法和实时荧光定量聚合酶链反应(RT-qPCR)检测癌组织和癌旁组织中ZEB2和E-Cad蛋白及mRNA的表达。收集所有患者的临床病历资料。对所有患者随访5年,记录生存情况。采用Kaplan-Meier生存曲线分析ZEB2、E-Cad表达与乳腺癌患者生存率之间的关系。采用Cox比例风险模型分析乳腺癌患者5年生存率的影响因素。采用受试者工作特征(ROC)曲线分析ZEB2和E-Cad判断乳腺癌预后的效能。结果 癌组织ZEB2阳性率显著高于癌旁组织(P<0.05),E-Cad阳性率显著低于癌旁组织(P<0.05)。乳腺癌组织ZEB2表达与E-Cad表达呈负相关(r=-0.265,P=0.018)。癌组织ZEB2 mRNA相对表达量显著高于癌旁组织(P<0.05),E-Cad mRNA相对表达量显著低于癌旁组织(P<0.05)。ZEB2表达与肿瘤直径、淋巴结转移、TNM分期、人表皮生长因子受体2(HER-2)表达有关(P<0.05),E-Cad表达与淋巴结转移、TNM分期、雌激素受体(ER)表达、孕激素受体(PR)表达、HER-2表达有关(P<0.05)。癌组织ZEB2阴性乳腺癌患者的5年总生存率显著高于阳性患者(P<0.05),E-Cad阳性乳腺癌患者的5年总生存率高于阴性患者(P<0.05)。Cox比例风险模型分析结果显示,淋巴结转移、TNM分期、ZEB2表达、E-Cad表达是影响乳腺癌患者预后的因素[风险比(HR)分别为3.47、6.49、2.35、0.15]。ROC曲线分析结果显示,ZEB2、E-Cad单项检测和联合检测判断乳腺癌患者5年生存的曲线下面积分别为0.618、0.638、0.827。结论 乳腺癌组织ZEB2和E-Cad蛋白表达异常,或可作为乳腺癌预后评估的指标。

Objective To analyze the expressions and prognostic values of E-box binding zinc finger protein 2(ZEB2) and epithelial-cadherin(E-Cad) in breast cancer tissues. Methods Tissue specimens of 80 patients with pathologically confirmed breast cancer and normal tissue specimens of adjacent tissues(≤3 cm from cancer tissues)were collected. Immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction(RTqPCR) were used to determine the expressions of ZEB2 and E-Cad proteins and their mRNA in breast cancer tissues and corresponding adjacent tissues. The medical history data of all the patients were collected. All the patients were followed up for 5 years,and the survival status was recorded. Kaplan-Meier survival curve was used to analyze the relations between the expressions of ZEB2 and E-Cad and the survival rate of breast cancer patients. Cox proportional hazard model was used to analyze the prognostic factors of 5-year survival rate of patients with breast cancer. Receiver operating characteristic(ROC) curve was used to analyze the efficacy of ZEB2 and E-Cad in breast cancer.Results The positive rate of ZEB2 in cancer tissues was higher than that in adjacent tissues(P<0.05),while the positive rate of E-Cad in cancer tissues was lower than that in adjacent tissues(P<0.05). There was a negative correlation between the expressions of ZEB2 and E-Cad in breast cancer tissues(r=-0.265,P=0.018). The relative expression of ZEB2 mRNA in cancer tissues was higher than that in adjacent tissues,while the relative expression of E-Cad mRNA in cancer tissues was lower than that in adjacent tissues. The expression of ZEB2 was related to tumor diameter,lymph node metastasis,TNM stage and human epidermal growth factor receptor-2(HER-2) expression.The expression of E-Cad was related to lymph node metastasis,TNM stage,estrogen receptor(ER) expression,progesterone receptor(PR) expression and HER-2 expression. The 5-year survival rates of ZEB2-negative and E-Cad-positive breast cancer patients was higher than that of ZEB2-positive and E-Cad-negative breast cancer patients,respectively(P<0.05). Cox proportional hazard model analysis showed that lymph node metastasis,TNM stage,ZEB2 expression and E-Cad expression were the prognostic factors for breast cancer patients [hazard ratio(HR)=3.47,6.49,2.35 and 0.15,respectively]. The results of ROC curve analysis showed that the areas under the curves for judging the 5-year survival of breast cancer by single and combined determinations of ZEB2 and E-Cad were 0.618,0.638 and 0.827,respectively. Conclusions ZEB2 and E-Cad proteins are abnormally expressed in breast cancer tissues,which may be used to evaluate the prognosis of breast cancer.