口腔白斑抑癌基因DAPK和TIG1高甲基化表达研究

摘要 目的：探讨抑癌基因DAPK、TIG1高甲基化在口腔白斑中表达状态及其对口腔癌发生发展中的作用。方法：取77例口腔白斑、32例口腔鳞癌、32份正常口腔黏膜组织，用实时定量甲基化特异性PCR技术检测组织中DAPK、TIG1高甲基化表达并进行统计学分析。结果：DAPK在口腔鳞癌组织中高甲基化表达率为46.9%，表达量为（0.0728±0.1617），明显高于其在口腔白斑组织（19.5%，0.0070±0.0172）和口腔正常组织（18.8%，0.0021±0.0050）中的表达，差异有统计学意义（P<0.05）。DAPK高甲基化表达与口腔白斑组织上皮异常增生程度相关，上皮增生高风险组相对于低风险组DAPK高甲基化表达风险增加（OR，1.013；95% CI，1.004-1.023；P=0.004）。TIG1高甲基化在正常组织中未表达，在口腔鳞癌组织和口腔白斑组织表达为（28.1%，0.0174±0.0440）和（27.3%，0.0035±0.0076），与正常组织相比具有统计学意义（P<0.05）。结论：抑癌基因 DAPK、TIG1高甲基化有望成为口腔黏膜癌变早期标志物。

Hypermethylation of DAPK and TIG1 in Oral Leukoplakia

ABSTRACT Objective: To detect promoter hypermethylation status of tumor suppressor genes of DAPK and TIG1 in oral leukoplakia (OLK) and explore its potential roles in oral carcinogenesis. Methods: DAPK and TIG1 hypermethylation were evaluated in 77 OLK, 32 oral squamous cell carcinomas (OSCC) and 40 normal tissues by quantitative methylation-specific PCR (QMSP). Results: It was found that DAPK were hypermethylated in OSCC. The frequency (46.9%) and the quantity (0.0728±0.1617) of DAPK hypermethylation in OSCC was significant higher than those in OLK and normal tissues (OLK: 19.5%, 0.0070±0.0172; nornal tissues: 18.8%, 0.0021±0.0050, P<0.05). Furthermore, DAPK hypermethylation was significantly correlated with epithelial dysplasia. Compared with the low malignant potential group of OLK patients(LMP), the high malignant potential group (HMP) was more likely to express increased gene hypermethylation of DAPK (OR, 1.013; 95% CI: 1.004-1.023; P=0.004). No hypermethylation of TIG1 was found in normal tissues. The frequency (OSCC: 28.1%; OLK: 27.3%) and the quantity (OSCC: 0.0174±0.0440; OLK: 0.0035±0.0076) of TIG1 hypermethylation were both higher than those in normal tissues(P<0.05). Conclusion: Our data suggested that DAPK and TIG1 hypermethylations were associated with oral precancer and may be useful as early detection markers for oral cancer.