宫颈癌组织中FHIT基因5'端CpG岛甲基化及其与基因失活的关系

Correlation between Methylation of 5′-CpG Islands and Inactivation of FHIT Gene in Cervical Cancer

背景与目的:脆性组氨酸三联基因(fragile histidine triad gene,FHIT)作为抑癌基因与多种实体瘤的发生有关,并在多种肿瘤中因甲基化而失活。本研究拟探讨宫颈癌组织中FHIT基因5'端CpG岛甲基化状况及其与基因失活的关系。方法:采用甲基化特异性聚合酶链反应(methylation鄄specificPCR,MSP)和免疫组织化学法分别检测10例正常宫颈鳞状上皮、40例宫颈癌组织中FHIT基因5'端CpG岛的甲基化发生状况和FHIT蛋白表达情况。结果:(1)正常宫颈鳞状上皮组织中未发现存在FHIT基因甲基化状态,而宫颈癌组织中FHIT基因5'端CpG岛的甲基化率为40.0%(16/40);(2)临床Ⅱ期宫颈癌病例中FHIT基因甲基化的发生率为56.5%(13/23),明显高于Ⅰ期的14.3%(2/14)(P<0.05);(3)宫颈癌组织中存在FHIT蛋白表达降低或缺失,阳性率仅为30.0%(12/40),显著低于正常宫颈组织的100.0%(10/10)(P<0.05)。结论:FHIT基因5'端CpG岛甲基化是宫颈癌中该基因失活的机制之一,可能与宫颈癌的发生发展有关。

BACKGROUND & OBJECTIVE: Fragile histidine triad (FHIT) gene, a tumor suppressor gene, correlates with tumorigenesis of many solid tumors, and may be inactivated via methylation. This study was designed to explore relationship of methylation of 5′-CpG islands with inactivation of FHIT gene in cervical cancer. METHODS: Methylation of 5′-CpG islands in 10 normal cervical squamous epithelial tissues, and 40 cervical cancer tissues was detected with methylation specific polymerase chain reaction (MSP), protein expression of FHIT was detected with immunohistochemistry, and their correlations with clinicopathologic features of cervical cancer were statistically analyzed. RESULTS: (1) The 5′-CpG islands methylation rate of FHIT gene in cervical cancer tissues was 40.0% (16/40), while no methylation of FHIT gene was found in normal cervical tissues. (2) The methylation rates of FHIT gene in cervical cancer of stage Ⅰ was 14.3% (2/14), significantly lower than that in cervical cancer of stage Ⅱ (56.5%, 13/23) (P<0.05). (3) Expression of FHIT protein in cervical cancer was 33.0% (12/40), significantly lower than that in normal cervical tissue (100%, 10/10) (P<0.05). CONCLUSION: The 5′-CpG islands methylation may play an important role in inactivation of FHIT gene, and may be related with tumorigenesis of cervical cancer.