肝动脉化疗栓塞术后原发性肝癌患者的肠道菌群变化  

Changes in intestinal flora in patients with primary liver cancer after transcatheter arterial chemoembolization

作　　者：李科志[1] 韦家康 韩志伟 仇雯霞 陈欣欣 黄山[3] 何剑波[4] 邬国斌[3] 陈闯[5] LI Kezhi;WEI Jiakang;HAN Zhiwei(Department of Research, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China)

机构地区：[1]广西医科大学附属肿瘤医院实验研究部,南宁530021 [2]广西医科大学附属肿瘤医院研究生院,南宁530021 [3]广西医科大学附属肿瘤医院肝胆外科,南宁530021 [4]广西医科大学附属肿瘤医院肿瘤科,南宁530021 [5]广西医科大学附属肿瘤医院中医科,南宁530021 [6]贵港市人民医院,广西贵港537100 [7]广西医科大学第一附属医院研究生院,南宁530021

出　　处：《临床肝胆病杂志》2020年第5期1043-1049,共7页Journal of Clinical Hepatology

基　　金：国家自然科学基金地区项目(81560726);广西科技计划项目-重点研发计划(AB18126066);中央引导地方科技发展专项(桂科ZY1949017);南宁市科学研究与技术开发计划(20193116);广西高校中青年教师科研基础能力提升项目(2020KY03048)。

摘　　要：目的对比分析原发性肝癌患者及经肝动脉化疗栓塞术(TACE)治疗前后肠道菌群的多样性变化及菌群结构差异。方法选取2018年9月-2019年1月广西医科大学附属肿瘤医院原发性肝癌患者65例(其中接受TACE治疗20例),健康体检者27例。高通量16S rDNA测序方法分析患者便菌群结构,Anosim、LEf Se软件与R语言stats包分析菌群组间物种相对丰度、组间物种多样性、群落差异、进化分支等差异。符合正态性及方差齐的计量资料两组间比较采用t检验;不符合正态分布计量资料组间比较采用Kruskal-Wallis U检验;计数资料组间比较采用χ2检验。相关性分析采取Spearman秩相关性分析。结果在门水平,各组的最大优势菌均为拟杆菌门(Bacteroidetes)、厚壁菌门(Firmicutes),两者占比之和在健康组>90%,在原发性肝癌组及TACE治疗组中占比均>80%。拟杆菌门在健康组、原发性肝癌组、TACE治疗组占比分别为48.44%、44.96%、48.60%,厚壁菌门在各组占比分别为47.09%、38.15%、33.93%,拟杆菌门、厚壁菌门相对丰度在肝癌组均低于健康组;此外,变形菌门(Proteobacteria)及梭杆菌门(Fusobacteria)相对丰度在肝癌组及TACE治疗组中占比均高于健康组;其余菌门虽有所变化,但占比均<0.5%。健康组物种丰富度Observed species(264±47 vs 230±64,t=2.499,P=0.014)及ACE值(284.11±50.82 vs 252.96±67.58,t=2.158,P=0.034)均大于原发性肝癌组。Between组(原发性肝癌组+健康组)的秩较原发性肝癌组及健康组高,R>0,健康组及原发性肝癌组肠道菌群组间结构差异大于组内差异(P<0.05);Between组(TACE术前+术后)的秩低于TACE术前组,R<0,TACE治疗前与治疗后组内结构差异大于组间结构差异(P>0.05)。原发性肝癌患者肠内机会致病菌与Child-Turcotte-Pugh评分、TBil、ALT、AST存在相关性(r值分别为0.245、0.421、0.327、0.446,P值分别为0.049、<0.001、0.008、<0.001),潜在益生菌与Child-Turcotte-Pugh评分、TObjective To investigate the changes in the diversity and structure of intestinal flora in patients with primary liver cancer after transcatheter arterial chemoembolization(TACE).Methods A total of 65 patients with primary liver cancer(among whom 20 received TACE)who were treated in The Affiliated Tumor Hospital of Guangxi Medical University from September 2018 to January 2019 were enrolled,and 27 individuals who underwent physical examination were enrolled as healthy group.High-throughput 16S rDNA sequencing was used to analyze the structure of fecal bacterial communities,and Anosim,LEfSe software,and R language stats package were used to analyze the differences in the relative abundance,diversity,community,and evolutionary branching of intestinal flora between groups.The t-test was used for comparison of normally distributed continuous data with homogeneity of variance between groups,and the Kruskal-Wallis U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.The Spearman rank correlation test was used for correlation analysis.Results At the phylum level,the dominant bacteria were Bacteroidetes and Firmicutes in each group,which accounted for>90%in the healthy group and>80%in the primary liver cancer group and the TACE treatment group.Bacteroidetes accounted for 48.44%,44.96%,and 48.60%,respectively,in the healthy group,the primary liver cancer group,and the TACE treatment group,and Firmicutes accounted for 47.09%,38.15%,and 33.93%,respectively,in the three groups,suggesting that the primary liver cancer group had significantly lower relative abundance of Bacteroidetes and Firmicutes than the healthy group;in addition,the primary liver cancer group and the TACE treatment group had significantly higher relative abundance of Proteobacteria and Fusobacteria than the healthy group;although there were changes in the other phyla of bacteria,these bacteria accounted for<0.5%.Compared with the primary live

关 键 词：肝肿瘤 化学栓塞 治疗性 胃肠道微生物组 物种多样性 

分 类 号：R735.7[医药卫生—肿瘤]