错配修复基因hMSH2表达水平与上皮性卵巢癌患者的临床预后相关

The expression of mismatch repair gene hMSH2 is associated with clinical prognosis in patients with epithelial ovarian cancer

目的:探讨错配修复基因hMSH2表达与上皮性卵巢癌(epithelial ovarian cancer,EOC)患者临床预后的相关性。方法:采用实时荧光定量PCR法检测150例EOC患者肿瘤组织中hMSH2 mRNA的表达水平,免疫组织化学法检测86例肿瘤组织中hMSH2蛋白的表达水平。分析hMSH2 mRNA表达与EOC患者临床病理特征的相关性;Wilcoxon秩和检验比较铂耐药组患者和铂敏感组患者肿瘤组织中hMSH2 mRNA表达水平的差异;Kaplan-Meier法和COX回归模型分析hMSH2 mRNA表达与EOC患者预后的相关性。结果:EOC患者肿瘤组织中hMSH2 mRNA表达水平与临床分期、组织学分级和淋巴结转移明显相关(P<0.05)。铂耐药患者肿瘤组织中hMSH2 mRNA表达水平明显低于铂敏感患者(P=0.004);hMSH2 mRNA低表达可能明显降低EOC患者的无进展生存期(progression free survival,PFS)和总生存时间(overall survival,OS)(P值均<0.05);COX回归模型显示,hMSH2 mRNA表达水平可能是预测EOC患者OS的独立危险因素[风险比(hazard ratio,HR)=1.91,95%可信区间(confidence interval,CI)为1.85~2.31,P=0.033]。结论:肿瘤组织中hMSH2 mRNA表达水平与EOC患者的临床分期、组织学分级、淋巴结转移、铂类耐药以及预后密切相关。

Objective:To explore the correlation between the expression of mismatch repair gene human mutS homologue 2(hMSH2)and the clinical prognosis of patients with epithelial ovarian cancer(EOC).Methods:Real-time fluorescent quantitative PCR was used to detect the hMSH2 mRNA expression level in the tumor tissues of 150 EOC patients;Immunohistochemistry assay was used to detect the hMSH2 protein expression in tumor tissues of 86 EOC patients.The correlation between hMSH2 mRNA expression and clinicopathological characteristics of EOC patients was analyzed by Chi-square test.The difference of hMSH2 mRNA expression levels in tumor tissues of platinum-resistant and platinum-sensitive patients was compared using the Wilcoxon Rank Sum test.Kaplan-Meier analysis and COX proportional hazard model were performed to analyze the association of hMSH2 mRNA expression with the prognosis of EOC patients.Results:hMSH2 mRNA expression level was significantly correlated with FIGO stage,histological grade and lymph node metastasis(all P<0.05).The hMSH2 mRNA expression level in the platinum-resistant group was significantly lower than that in the platinum-sensitive group(P=0.004).The low expression of hMSH2 mRNA was significantly associated with shorter progression free survival(PFS)and overall survival(OS)in EOC patients(both P<0.05).Moreover,COX proportional hazard model showed that hMSH2 mRNA expression level was an independent risk factor predicting OS of EOC patients[hazard ratio(HR)=1.91;95%CI:1.85-2.31;(P=0.033)].Conclusion:The expression level of hMSH2 mRNA in tumor tissues is closely related to clinical stage,histological grade,lymph node metastasis,platinum resistance and prognosis of EOC patients.