卵巢癌组织中PCDH8基因启动子甲基化状态及其与患者临床特征的关系

The Methylation Status of PCDH8 Gene Promoter in Ovarian Cancer and Its Relationship with Clinical Characteristics

目的探讨卵巢癌组织中原钙黏蛋白-8(protocadherin-8,PCDH 8)甲基化状态及其临床意义。方法选取2013年1月至2014年1月我院收治的140例卵巢癌患者为研究对象。采用Western blot法检测卵巢癌组织、癌旁组织中PCDH8蛋白的表达。采用甲基化特异性PCR(MSP)检测卵巢癌组织中PCDH8甲基化状态。分析PCDH8甲基化状态与临床病理特征的相关性。Kaplan-Meier生存分析与多因素Cox危险模型分析PCDH8甲基化与卵巢癌患者预后的相关性。结果卵巢癌组织PCDH8蛋白量低于癌旁正常组织,差异有统计学意义(t=10.827,P=0.033)。卵巢癌组织中PCDH8基因启动子甲基化率为(75.71%,106/140)高于癌旁正常组织(7.86%,11/140),差异具有统计学意义(χ2=21.098,P<0.001)。PCDH8基因启动子甲基化率与患者的WHO组织学分级、淋巴结转移情况及TNM分期有关(P<0.05)。CDH8启动子甲基化的卵巢癌患者无复发生存率、无进展生存率、5年生存率短于PCDH8启动子非甲基化的卵巢癌患者,差异具有统计学意义(χ2=11.365,12.386,9.008,P<0.001,<0.001,0.026)。TNM分期与PCDH8基因甲基化是卵巢癌患者随访5年期间预后的危险因素。结论PCDH 8甲基化可能与卵巢癌进展及预后不良有关,可作为预测卵巢癌预后的潜在生物标志物。

Objective To investigate the methylation status of PCDH8 in ovarian cancer and its clinical significance.Methods 140 patients with ovarian cancer from January,2013 to January,2014 in our hospital were selected for the study.PCDH8 in the ovarian cancer tissues and para-carcinoma tissues were detected with western blot method.The methylation status of PCDH8 in the ovarian cancer tissues and para-carcinoma tissues was examined by methylation-specific PCR(MSP),and we then analyzed the correlations between PCDH8 methylation and clinicopatholocial features.Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis were used to investigate the correlation between PCDH8 methylation and prognosis of patients with ovarian cancer.Results The content of PCDH8 protein in ovarian cancer tissues was significantly lower than that in adjacent normal tissues(t=10.827,P=0.033).The methylation rate of PCDH8 gene promoter in ovarian cancer tissues(75.71%,106/140)was significantly higher than that in adjacent normal tissues(7.86%,11/140)(χ2=21.098,P<0.001).The methylation rate of PCDH8 gene promoter was related to WHO histology grade,lymph node metastasis and TNM stage(P<0.05).The recurrence-free survival rate,progression-free survival rate and 5-year survival rate in patients with methylated PCDH8 gene promoter were significantly shorter than those in patients with non-methylated PCDH8 gene promoter(χ2=11.365,12.386,9.008,P<0.001,<0.001,0.026).TNM stage and PCDH8 gene methylation were risk factors for prognosis in patients with ovarian cancer during 5 years of follow-up.Conclusion PCDH8 methylation might be associated with tumor progression and poor prognosis in NMIBC and can be used as a potential biomarker to predict the prognosis of patients with NMIBC.