CDH1基因甲基化状态与结直肠癌临床病理特征及预后的相关性分析

The correlation between CDH1 gene methylation status and clinical pathological characteristics and prognosis of colorectal cancer

目的检测原发性结直肠癌患者术中腹腔灌洗液悬浮细胞中的CDH1基因启动子所在5'-Cp G岛的异常甲基化,同时对其异常甲基化与临床病情发展、病理变化及术后预后的相关关系进行探讨。方法选取该院肿瘤科进行结直肠癌切除术的原发性结直肠癌患者,所有入选患者由专人进行跟踪随访。检测CDH1基因启动子所在5'-Cp G岛的异常甲基化,对其异常甲基化与临床病情发展、病理变化及术后预后的相关关系进行探讨。结果该研究共纳入患者184例,其中甲基化组86例,非甲基化组98例。对两组患者临床病理结果检查可知甲基化组肿瘤直径大于非甲基化组(P<0.001),甲基化组肿瘤浸润性所占比例高于非甲基化组(P<0.001),甲基化组肿瘤分化程度低于非甲基化组(P<0.001),甲基化组淋巴转移率、远处转移率高于非甲基化组(P<0.001,P=0.026),甲基化组临床TNM分期更晚(P<0.001)。根据随访结果显示非甲基化组患者生存率高于甲基化组患者(P<0.05)。Cox比例风险模型结果显示,患者肿瘤的大体分型、分化程度、侵袭程度和病理分期是影响生存预后的变量,其中腹腔灌洗液悬浮细胞CDH1基因甲基化是影响预后最重要的独立因素,RR=28.514。结论原发性结直肠癌患者腹腔灌洗液悬浮细胞CDH1基因甲基化程度提高,恶性程度高,预后差。

Objective To detect the CDH1 gene methylation of suspension cells in intraoperative abdominal lavage fluid from colorectal cancer patients,and to examine its association with clinicopathology and prognosis. Methods Real-time methylation-specific polymerase chain reaction( q-MSP) Was used to investigate the methylation status of the CDH1 gene promoter 5'-Cp G islands from intraoperative abdominal lavage fluid in 184 patients with colorectal cancer. The associations between methylation of CDH1 genes and clinieopathologic features and prognosis were investigated. Results Among the 184 colorectal cancer patients,aberrant methylation of CDH1 gene was detected in 86 patients. Significant associations were found between CDH1 methylation status and tumor size,growth pattern,differentiation,distant metastasis,and clinical staging( all P < 0. 05). The median progression-free survival was 28. 6 months for CDH1 methylation group and 42. 3 months for non—methylated group,and the difference Was statistically significant( P < 0. 01).The factors of Dukes stage,gross tumor configuration,intramural spread,differentiation degree and CDH1 methylation status in intraoperative peritoneal lavage fluid were available independent prognostic factors through multivariate analysis. And CDH1 methylation status in intraoperative peritoneal lavage fluid was the most important factor,RR = 28. 514. Conclusions Colorectal cancer patients with aberrant methylation of 5'-Cp G of CDH1 gene promoter of suspension cells in abdominal lavage have higher malignancy,more metastasis and worse prognosis.