食管鳞癌患者血浆中DAPK基因异常甲基化及临床意义研究

Abnormal Methylation of Death Association Protein Kinase(DAPK) Gene in Plasma of Patients with Esophageal Squamous Cell Carcinoma and Its Clinical Significance

[目的]研究食管鳞癌患者癌组织及血浆中DAPK基因甲基化的情况,探讨血浆中DAPK甲基化检测在食管鳞癌早期诊断、治疗、预后评估中的作用。[方法]食管鳞癌患者155例,分别提取血浆、癌组织及癌旁正常组织中DAPK基因的DNA,并结合临床病理以及随访结果,进行DAPK甲基化分析。[结果]癌组织与癌旁正常组织中DAPK的甲基化率差异有统计学意义(P=0.000),癌组织和血浆DAPK基因的甲基化在是否淋巴结转移、是否远处转移、不同分期时差异均有统计学意义(P<0.05)。癌组织和血浆中DAPK基因甲基化的相关系数r为0.849(P<0.000)。癌组织中和血浆中DAPK基因非甲基化患者具有明显的生存优势(P均为0.000)。Cox回归分析显示血浆DAPK甲基化是食管鳞癌患者生存的独立影响因子。[结论]食管鳞癌癌组织和血浆中DAPK基因甲基化均与肿瘤分期、淋巴结转移、远处转移相关;癌组织和血浆中DAPK基因甲基化有显著相关性,血浆中DAPK高甲基化可作为食管鳞癌预后不良的生物标志物。

[Purpose]To investigate the status of death association protein kinase（DAPK）methylation in cancer tissue and plasma in patients with esophageal squamous cell carcinoma（ESCC）,and to assess the role of plasma DAPK methylation detection for early diagnosis,treatment and prognosis in patients with ESCC.[Methods] DAPK DNA was extracted from cancer tissues,cancer adjacent tissues and plasma from 155 cases with ESCC respectively,and correlation of DAPK methylation with clinicopathological and follow-up results was analyzed.[Results] DAPK methylation was significantly different between cancer tissues and cancer adjacent tissues（P=0.000）.DAPK methylation in both cancer tissues and plasma was statistically significant between positive lymph node and negative lymph node,distant metastasis and non distant metastasis,and different stages（P0.05）.The correlation coefficient of DAPK methylation between cancer tissue and plasma was 0.849（P0.000）.Patients with DAPK nonmethylation in cancer tissues and plasma were superior survival to DAPK methylation patients（P=0.000,P=0.000）,Cox regression analysis showed that plasma DAPK methylation was an independent influencing factor for survival in patients with ESCC.[Conclusion] DAPK methylation of cancer tissues and plasma in patients with ESCC correlate with tumor stage,lymph node metastasis and distant metastasis.DAPK methylation between cancer tissues and plasma has significant correlation.Plasma DAPK methylation might be used as biological marker of poor prognosis for ESCC.