TFAP2E基因CpG岛甲基化状态与食管癌患者化疗疗效的关系研究

Relationship Between the CpG Island Methylation of TFAP2E and Chemotherapy in Patients with Esophageal Cancer

关键词:  食管癌  甲基化  TFAP2E  化疗疗效

Key words:  esophageal cancer  methylation  TFAP2E  chemotherapy response

摘要:

目的 探讨TFAP2E基因CpG岛甲基化状态与食管癌患者诊断及基于氟尿嘧啶类药物化疗疗效之间的关系。方法 搜集101例病理学明确诊断的食管癌组织及50例癌旁正常组织，通过荧光定量甲基化特异性PCR检测组织甲基化率。对其中75例晚期（IV期）患者接受基于氟尿嘧啶药物为基础化疗的疗效进行评价，并分析TFAP2E基因CpG岛甲基化状态和临床病理资料及化疗疗效间的关系。结果 肿瘤组织中TFAP2E甲基化的发生率高于正常组织（P<0.05）。TFAP2E甲基化率和肿瘤分化程度和淋巴结转移有关。TFAP2E甲基化状态和化疗疗效有关，Logistic回归分析表明低甲基化TFAP2E患者化疗效果明显优于高甲基化患者（OR=2.89，95% CI：1.57~5.37；P<0.05）。结论 TFAP2E基因CpG岛甲基化和接受基于氟尿嘧啶化疗食管癌患者疗效相关，可能成为预测化疗效果的有效生物标志。

Abstract:

OBJECTIVE To investigate the relationship between the CpG island methylation of TFAP2E and the diagnosis of patients with esophageal cancer based on fluorouracil chemotherapy. METHODS The 101 cases of esophageal carcinoma tissues and 50 normal tissues were collected. The methylation rate was detected by fluorescence quantitative methylation specific PCR. The efficacy of fluorouracil-based chemotherapy was evaluated in 55 patients with advanced stage (IV). And to analyze the relationship between the methylation status of TFAP2E gene CpG island and clinicopathological data and chemotherapy efficacy. RESULTS The TFAP2E methylation occurred at a significantly higher incidence rate in tumor tissues compared to adjacent nontumor tissues(P<0.05). Hypermethylation of TFAP2E occurred more frequently in tumors with lower differentiation grades and lymph node metastasis (P<0.05). The chemotherapy effect of hypermethylated TFAP2E patients was significantly lower than that of hypomethylated patients (OR=2.89, 95% CI:1.57-5.37; P<0.05). CONCLUSION The CpG island methylation of TFAP2E is associated with fluorouracil based chemotherapy in patients with esophageal cancer and may be an effective biomarker for predicting chemotherapy.