Ren C C, Miao X H, Yang B, Zhao L, Sun R, Song W Q
Department of Genetics, Central Hospital of Gynecology and Obstetrics, Tianjin, China.
Int J Gynecol Cancer. 2006 Sep-Oct;16(5):1862-7. doi: 10.1111/j.1525-1438.2006.00669.x.
Recent evidence suggests that tumor cells may release DNA into the serum and plasma of afflicted cancer patients. However, no report existed regarding the methylation status of the fragile histidine triad (FHIT) and E-cadherin genes in plasma samples of cervical cancer patients. Methylation-specific PCR (MSP) was employed to examine CpG island methylation of the FHIT and E-cadherin genes in 151 pretreatment plasma samples and 30 tumor tissue samples from cervical cancer patients. MSP products were cloned and sequenced. CpG island methylation of the FHIT and E-cadherin genes was detected in 30.46% and 39.74% of plasma samples, respectively, and in 53.33% and 60.0% of tissue samples, respectively. The total concordance rate of methylation between plasma samples and tissue samples in FHIT gene was 80.00% and that in E-cadherin gene was 76.66%. At least one of the two methylated genes was detected in 56.29% of plasma samples and 76.7% of tissue samples. The presence of both methylated genes was detected in 13.9% of plasma samples and 36.67% of tissue samples. We found that the higher the clinical stage and histologic grade, the higher the rate of methylation in both genes in plasma samples. CpG island methylation of the FHIT and E-cadherin genes is present in plasma of cervical cancer patients. Using the two genes as markers simultaneously may allow clinicians to diagnose and evaluate the effect of treatment earlier and using fewer invasive procedures.
近期证据表明，肿瘤细胞可能会将DNA释放到罹患癌症患者的血清和血浆中。然而，关于宫颈癌患者血浆样本中脆性组氨酸三联体（FHIT）和E-钙黏蛋白基因的甲基化状态尚无相关报道。采用甲基化特异性PCR（MSP）检测了151份宫颈癌患者治疗前血浆样本和30份肿瘤组织样本中FHIT和E-钙黏蛋白基因的CpG岛甲基化情况。对MSP产物进行克隆和测序。FHIT和E-钙黏蛋白基因的CpG岛甲基化在血浆样本中的检出率分别为30.46%和39.74%，在组织样本中的检出率分别为53.33%和60.0%。FHIT基因血浆样本与组织样本甲基化的总符合率为80.00%，E-钙黏蛋白基因的为76.66%。56.29%的血浆样本和76.7%的组织样本中检测到两个甲基化基因中的至少一个。13.9%的血浆样本和36.67%的组织样本中检测到两个甲基化基因均存在。我们发现，临床分期和组织学分级越高，血浆样本中两个基因的甲基化率越高。宫颈癌患者血浆中存在FHIT和E-钙黏蛋白基因的CpG岛甲基化。同时使用这两个基因作为标志物可能使临床医生能够更早地进行诊断和评估治疗效果，且采用的侵入性操作更少。
