Fibulin-1基因启动子区域甲基化与食管癌的关系研究

Relationship of promoter region methylation of Fibulin-1 gene and esophageal cancer

目的:检测食管癌Fibulin-1基因启动子区域甲基化的情况,探讨其相关的临床意义。方法:选取黄石市中心医院2014年1月至2016年2月收治的食管鳞状细胞癌患者96例,另取同期黄石市中心医院因食管良性病变手术切除的食管组织40例作为对照。Fibulin-1基因启动子甲基化使用亚硫酸盐修饰后PCR检测。免疫组织化学检测显示Fibulin-1蛋白表达。结果:食管癌患者中Fibulin-1基因启动子甲基化阳性率为36.5%,显著高于对照组的15.0%(χ2=2.517,P=0.036)。免疫组织化学检测显示Fibulin-1基因启动子甲基化标本中Fibulin-1蛋白阳性表达率为90.2%。食管癌患者男女性别和不同年龄之间Fibulin-1基因启动子甲基化率无显著性差异(P>0.05)。Ⅲ,Ⅳ临床分期患者Fibulin-1基因启动子甲基化率为43.1%,显著高于Ⅰ,Ⅱ临床分期患者的28.9%(χ~2=2.4 2 6,P=0.0 4 6)。肿瘤有淋巴结转移患者Fibulin-1基因启动子甲基化率为44.4%,显著高于无淋巴结转移患者的26.2%(χ2=2.438,P=0.041)。肿瘤中、低分化患者Fibulin-1基因启动子甲基化率为42.6%,显著高于高分化患者的25.7%(χ~2=2.431,P=0.043)。结论:Fibulin-1基因启动子在食管癌组织中高甲基化,Fibulin-1基因启动子高甲基化与食管癌的临床分期、肿瘤分化程度以及有无淋巴结转移密切相关。

Objective： To detect promoter region methylation ofFibulin-1 gene in esophageal cancer and explore its clinical significance. Methods： Ninety-six patients of esophageal cancer admitted from January 2014 to February 2016 in Huangshi Central Hospital were enrolled in this study. Another 40 cases of benign esophageal tissues were used as control. Fibulin-1 gene promoter was modified by bisulfite and methylation was detected using PCR analysis. Fibulin-1 protein expression was detected by immunohistochemistry. Results： The positive rate of Fibulin-1 gene promoter methylation in patients with esophageal cancer was 36.5%, which was significantly higher than that of 15.0% in control group （Xz=2.517, P=0.036）. The positive expression rate of Fibulin-1 protein in the promoter methylation of Fibulin-1 gene was 90.2%. the positive rate of Fibulin-1 gene promoter methylation hasno significant difference in different gender and age in bladder cancer （P〉0.05）. The positive rate of Fibulin-1 gene promoter methylation in Ⅱ and 1V stage group was 43.1%, which was higher than that of 28.9% in I and Ⅱ stage group （Xz=2.426, P=0.046）. The positive rate ofFibulin-1 gene promoter methylation in lymph node metastasis group was 44.4%, which was higher than that of 26.2% in non-lymph node metastasis group （Kz=2.438, P=0.041）. The positive rate of Fibulin-1 gene promoter methylation in median and low differentiation group was 42.6%, which was higher than that of 25.7% in well-differentiation group （X2=2.431, P=0.043）. Conclusion： Hypermethylation ofFibulin-1 gene was detected in esophageal cancer, which was related to clinical stages, lymph node metastasis, and tumor differentiation of esophageal cancer.