胃癌及癌前病变患者肠道菌群变化及其与PI3K/AKT/mTOR信号通路相关性的研究  

Study on the changes of intestinal flora in patients with gastric cancer and precancerous lesions and its correlation with PI3K/AKT/mTOR signaling pathway

作　　者：刘源[1] 侯楠 高俊[1] LIU Yuan;HOU Nan;GAO Jun(Department of Gastrointestinal Oncology,Nanyang Second People's Hospital,Nanyang,473000,China)

机构地区：[1]南阳市第二人民医院胃肠肿瘤科,河南南阳473000

出　　处：《中国现代普通外科进展》2025年第2期119-124,共6页Chinese Journal of Current Advances in General Surgery

基　　金：南阳市2022年市级科技发展计划项目(KJGG079)。

摘　　要：目的:探讨胃癌及癌前病变患者肠道菌群变化及其与磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关性。方法:按倾向性评分匹配“邻近法”,比例为1∶1∶1,选取我院2022年9月至2024年3月收治的胃上皮内瘤变(GIN)患者45例(癌前组)、胃癌患者45例(胃癌组)以及健康体检中心的健康志愿者45例(对照组)作为研究对象,利用大便16S rRNA高通量测序检测肠道菌群。通过操作分类单元(OTU),比较3组肠道菌群α多样性分析、β多样性分析、菌落结构差异和线性判别效应分析(LEfSe),比较3组粪便PI3K/AKT/mTOR信号通路;采用Pearson法分析肠道菌群与PI3K/AKT/mTOR信号通路的相关性。结果:粪便样本测序共得到572个不同的OTU,其中3组共有的OTU287个,主成分分析结果显示,3组间两两比较差异均有统计学意义(P<0.05)。3组Chao、Shannon、Simpson、Observed指数比较,差异均无统计学意义(P>0.05);胃癌组肠道菌群物种丰度和构成较为分散,对照组则较接近,癌前组居于中间,3组间两两比较差异均有统计学意义(P<0.05)。LEfSe显著性分析显示,在门水平上,胃癌组、癌前组放线菌门、厚壁菌门丰度低于对照组,且胃癌组低于癌前组,而变形菌门、弯曲杆菌门、拟杆菌门丰度增加,且胃癌组高于癌前组;在属水平上,胃癌组大肠埃希菌-志贺菌属丰度高于对照组,拟杆菌属则低于对照组,差异均有统计学意义(P<0.05);胃癌组、癌前组PI3K mRNA、AKT mRNA、mTOR mRNA高于对照组,且癌前组高于对照组,差异均有统计学意义(P<0.05);Pearson相关性分析,肠杆菌目、大肠埃希菌-志贺菌属与PI3K mRNA、AKT mRNA、mTOR mRNA呈正相关,拟杆菌属与之呈负相关。结论:肠道菌群多样性、结构、丰度与胃癌癌前病变及其发生、进展相关,肠杆菌属、大肠埃希菌-志贺菌属与PI3K/AKT/mTOR信号通路基因表达均有一定相关性,可为临床判断癌Objective:Exploring gut microbiota alterations in gastric cancer and precancerous lesions and their Association with the PI3K/AKT/mTOR signaling pathway.Methods:According to the propensity score matching"proximity method"with a ratio of 1:1:1,45 patients with gastric intraepithelial neoplasia(GIN)(precancerous group),45 patients with gastric cancer(gastric cancer group),and 45 healthy individuals(health examination center)(control group)were selected as the research subjects.High-throughput sequencing of 16S rRNA was used to detect intestinal flora.By operating the taxonomic unit(OTU),the α diversity analysis,βdiversity analysis,colony structure differences,and linear discriminant effect analysis(LEfSe)of the three groups of intestinal flora were compared,and the PI3K/AKT/mTOR signaling pathway in the three groups of feces were compared.The correlation between intestinal flora and PI3K/AKT/mTOR signaling pathway was analyzed using Pearson's method.Results:A total of 572 different OTUs were obtained from fecal sample sequencing,of which 287 were shared by three groups.Principal component analysis showed that there were statistically significant differences between three groups(P<0.05).There was no significant difference in the Chao,Shannon,Simpson,and Observed indices among the three groups(P>0.05).The species abundance and composition of intestinal flora in the gastric cancer group were relatively dispersed,while those in the control group were closer.The precancerous group was in the middle,and there were statistically significant differences between the three groups(P<0.05).The LEfSe significance analysis showed that at the phylum level,the abundance of Actinobacteria and Firmicutes in the gastric cancer group and precancerous group was lower than that in the control group,and the gastric cancer group was lower than the precancerous group.However,the abundance of Proteobacteria,Campylobacteria,and Bacteroidetes increased,and the gastric cancer group was higher than the precancerous group;At the genus level,th

关 键 词：胃肿瘤 肠道菌群 PI3K/AKT/mTOR信号通路 

分 类 号：R735.2[医药卫生—肿瘤]