阑尾切除改变肠道菌群对结直肠癌预后影响的临床研究

Clinical study of the effect of intestinal flora alteration induced by appendectomy on prognosis of colorectal cancer

目的:探究既往阑尾切除对结直肠癌预后的影响及可能存在机制。方法:回顾性收集2013年1月至2016年12月西安交通大学第一附属医院收治的763例结直肠癌患者的临床及病理信息,根据肿瘤诊断前是否存在阑尾切除史,分为阑尾切除组(89例)和非阑尾切除组(674例),分析比较两组患者的总体生存率,以及既往阑尾切除史与结直肠癌患者预后的关系。应用阑尾切除后结直肠癌诱导小鼠模型,通过实时荧光定量聚合酶链式反应(qPCR)比较其粪便中拟杆菌属(Bacteroides)、普氏菌属(Prevotella)、布氏菌属(Blautia)相对丰度。结果:阑尾切除组患者的3、5年总体生存率均明显低于非阑尾切除组(61.8%vs.75.1%,46.4%vs.69.3%),差异具有统计学意义(χ^(2)=13.777,P<0.05);阑尾切除是结直肠癌预后独立危险因素(HR=1.475,95%CI:1.030~2.114)。阑尾切除后行氧化偶氮甲烷(AOM)+葡聚糖硫酸钠(DSS)诱导发生结直肠癌的小鼠,其粪便中显著富集拟杆菌属、普氏菌属,而布氏菌属丰度明显降低。结论:阑尾切除可能是结直肠癌不良预后的独立危险因素,其潜在机制和阑尾切除导致某些致癌致炎细菌在肠道中富集相关。

Objective:To assess the association between appendectomy and prognosis of secondary colorectal cancer.Methods:We retrospectively reviewed the data of 763 patients with colorectal cancer in The First Affiliated Hospital of Xi’an Jiaotong University from January 2013 to December 2016.Based on the inclusion and exclusion criteria,89 patients who underwent appendectomy were included in the appendectomy group and 674 patients who did not undergo appendectomy were included in the non-appendectomy group.Overall survival rates were compared between the two groups,and the association between appendectomy and prognosis prediction was evaluated.Using the murine appendectomy model of chronic colitis-associated colorectal cancer,the relative abundance of Bacteroides,Prevotella,and Blautia in the feces of mice was compared using real-time fluorescent quantitative polymerase chain reaction(qPCR).Results:The 3-and 5-year overall survival rates were significantly lower in the appendectomy group than in the non-appendectomy group(61.8%vs.75.1%and 46.4%vs.69.3%,respectively),and the differences between the two groups were statistically significant(χ^(2)=13.777,P<0.05).The analysis showed that appendectomy was an independent prognostic risk factor for colorectal cancer(HR=1.475,95%CI:1.030~2.114).The abundance of Prevotella and Bacteroides was higher and that of Blautia was lower in the feces of mice with colorectal cancer induced by azoxymethane(AOM)+dextran sulfate sodium(DSS)after appendectomy.Conclusions:Appendectomy may be an independent risk factor for poor prognosis of colorectal cancer,and its potential mechanism is related to the enrichment of some inflammation-related bacteria in gut flora structure caused by appendectomy.