宫颈癌组织中RASSF1A基因启动子甲基化对其表达水平的影响及临床意义

Effect of RASSF1A gene promoter methylation on its expression level in cervical cancer tissue and its clinical significance

目的 研究宫颈癌组织中RAS相关区域家族1A基因（RASSF1A）启动子甲基化水平和RASSF1A基因mRNA表达水平,分析其与宫颈癌临床病理参数的关系及临床意义.方法 收集40例宫颈癌组织及相应癌旁组织,采用巢式特异性甲基化方法检测RASSF1A基因启动子甲基化水平,采用实时荧光定量PCR（qRT-PCR）检测宫颈癌和癌旁组织中RASSF1A基因mRNA表达水平.结果 宫颈癌组织中RASSF1A基因mRNA表达水平（0.26±0.05）显著低于癌旁组织（0.28±0.03）,差异有统计学意义（t=2.27,P=0.026）;宫颈癌组织中RASSF1A基因启动子区的甲基化率（0.71%±0.04%）显著高于癌旁组织（0.66%±0.03%）,差异有统计学意义（t=6.78,P=0.000）;RASSF1A基因mRNA表达水平与病理分化程度（t=3.31,P=0.002）、国际妇产科联合会（FIGO）分期（t=2.13,P=0.040）、淋巴结转移（t=2.56,P=0.015）、浸润深度（t=2.93,P=0.006）有关;RASSF1A基因启动子区的甲基化水平与病理分化程度（t=2.08,P=0.045）、FIGO分期（t=2.66,P=0.011）、淋巴转移（t=2.22,P=0.033）、浸润深度（t=2.12,P=0.041）有关.结论 宫颈癌组织中RASSF1A基因启动子甲基化和RASSF1A基因mRNA的表达水平与宫颈癌的恶性程度相关,RASSF1A基因甲基化水平有望成为宫颈癌转移风险的重要指标.

Objective To research the promoter methylation level of RAS association domain family 1A （RASSF1A） and RASSF1A gene mRNA expression level in cervical cancer tissue, and to analyze their relationships with clinicopathological parameters of cervical cancer and the clinical significance.Methods The RASSF1A gene promoter methylation and RASSF1A gene mRNA were detected respectively by methylation specific PCR and quantitative real-time PCR method in 40 cases of cervical cancer tissues and corresponding adjacent tissues.Results RASSF1A mRNA expression level in cervical cancer （0.26±0.05） was significantly lower than that in adjacent tissues （0.28±0.03）, and the difference was statistically significant （t=2.27, P=0.026）.The methylation rate of RASSF1A gene promoter region （0.71%±0.04%） was significantly higher than that in adjacent tissues （0.66%± 0.03%）, and the difference was statistically significant （t=6.78, P=0.000）.The expression of RASSF1A mRNA was significantly correlated with pathological differentiation （t=3.31, P=0.002）, International Federation of Gynecology and Obstetrics （FIGO） stage （t=2.13, P=0.040）, lymphatic metastasis （t=2.56, P=0.015）.The promoter methylation level of RASSF1A gene was significantly correlated with pathological differentiation （t=2.08, P=0.045）, FIGO stage （t=2.66, P=0.011）, lymphatic metastasis （t=2.22, P=0.033）, depth of invasion （t=2.12, P=0.041）.Conclusion The RASSF1A gene promoter region methylation level and the RASSF1A gene mRNA expression level are associated with the malignant degree of cervical carcinoma.The RASSF1A gene promoter region methylation level may be used as a reference indicator for predicting the risk of metastasis of cervical cancer.