Six1基因启动子未甲基化在宫颈癌病情及预后评估中的价值

Significance of low level methyltion of Six1 gene promoter in the assessment of disease condition and prognosis for cervical cancer

目的研究Six1基因启动子未甲基化在宫颈癌病情及预后评估中的价值。方法选择宫颈癌患者(CER组)和正常健康女性(CON组)各80例为研究对象,采用甲基化特异性PCR(MSP法)检测CER组肿瘤组织、癌旁正常组织及CON组宫颈活检组织Six1基因启动子甲基化状态,分析Six1基因启动子甲基化与临床病理因素的关系,比较CER组中Six1基因启动子甲基化和未甲基化患者术后2年死亡率和无进展生存期(PFS)的差异。结果 CER组肿瘤组织Six1基因启动子甲基化率低于癌旁组织和CON组,差异有统计学意义(P﹤0.05),而CER组癌旁组织与CON组的Six1基因启动子甲基化率差异无统计学意义(P﹥0.05)。CER组肿瘤组织Six1基因启动子甲基化率在年龄和病理类型中的差异均无统计学意义(P﹥0.05),在HPV感染、分化程度、肿瘤最大径、淋巴结转移、远处转移和FIGO分期中差异有统计学意义(P﹤0.05)。CER组Six1启动子甲基化患者2年病死率低于启动子未甲基化患者,PFS高于启动子未甲基化患者,差异均有统计学意义(P﹤0.05)。结论宫颈癌发病机制可能与Six1基因启动子甲基化缺失有关,Six1基因启动子未甲基化在宫颈癌病情及预后评估中具有重要价值。

Objective To study the clinical significance of low level methylation of Six1 gene promoter in the assess-ment of disease condition and prognosis for cervical cancer. Method Patients with cervical carcinoma （CER group） and healthy women （CON group） were enrolled in the study. Methylation-specific PCR was used to detect the cervical cancer tissues and adjacent normal tissues in CER group and methylation of Six1 gene promoter in biopsies of CON group. The relationship between clinic-pathological factors and methylation of Six1 gene promoter was analyzed. The 2-year mortali-ty and disease-free survival （DFS） between cases with and without Six1 gene promoter methylation were compared. Re-sult The methylation rate in CER group’s tumor tissues was significantly lower than that in CER group’s normal adja-cent tissues and that in CON group （P〈0.05）, while the methylation rate in normal adjacent tissues of CER group was sim-ilar with that in CON group （P〉0.05）. There was no significant difference observed regarding age or pathologic type for methylation rate of Six1 gene promoter in tumor tissue of CER group （P〉0.05）, while HPV infection, histology differenti-ation, maximum tumor diameter, lymph node metastasis, distant metastasis and Figo staging were significantly correlated with the methylation rate （P〈0.05）. Patients with Six1 gene promoter methylation had lower 2-year mortality rate, and lon-ger PFS than those without methylation, and the differences were of statistical significance （P〈0.05）. Conclusion Low level methylation of Six1 gene may be the underlying mechanism of cervical cancer development, and it is of clinical sig-nificance in the assessment of disease condition and prognosis for cervical cancer.