MLH1蛋白与近端散发性结肠癌瘤内菌群特征关系的生物信息学分析  

Bioinformatics analysis of the relationship between MLH1 protein and tumor microflora characteristics in proximal sporadic colon cancer

作　　者：蒋萍[1] 朱安超[1] 刘营营 李宗敏[1] 刘玉艳[1] 单景军[1] 何英[3] JIANG Ping;ZHU Anchao;LIU Yingying;LI Zongmin;LIU Yuyan;SHAN Jingjun;HE Ying(Department of Pathology,Harbin First Hospital,Harbin 150010,China;Department of Pathology,Heilongjiang Provincial Hospital,Harbin 150036,China;Department of Gastroenterology,Harbin First Hospital,Harbin 150010,China)

机构地区：[1]黑龙江省哈尔滨市第一医院病理科,黑龙江哈尔滨150010 [2]黑龙江省医院病理科,黑龙江哈尔滨150036 [3]黑龙江省哈尔滨市第一医院消化科,黑龙江哈尔滨150010

出　　处：《中国普通外科杂志》2024年第4期592-602,共11页China Journal of General Surgery

基　　金：黑龙江省卫生健康委科技计划基金资助项目(20210101040241)。

摘　　要：背景与目的:mutL同源物1(MLH1)基因的突变会导致DNA错配修复(MMR)系统失活,从而增加结直肠癌的发生风险。此外,越来越多的研究表明,肠道菌群的组成和功能异常与结直肠癌的发生和发展密切相关。然而,MLH1蛋白表达与肠道菌群是否有关联目前尚不十分明确。因此,本研究通过分析中国东北地区不同MLH1蛋白表型近端散发性结肠癌(SCC)患者的肿瘤组织中微生物组的差异,探讨两者之间的潜在关系。方法:收集黑龙江省哈尔滨市第一医院和黑龙江省医院2020—2021年407例近端SCC肿瘤组织样本与临床资料,用免疫组化法筛选出其中MLH1蛋白缺失病例(缺失组)与MLH1蛋白完整病例(对照组)。采用16S rRNA基因测序技术,对提取的肠道肿瘤组织内微生物DNA,进行生物信息学分析,并分析临床病理特征以及特定类群的物种与菌群多样性的关系。结果:共筛选出缺失组病例20例,对照组18例,初步临床数据分析显示,肿瘤越大,MLH1蛋白缺失的风险越高(P<0.05)。不同MLH1状态下肿瘤组织内菌群的α多样性除Shannon指数外(P=0.042),其他指数差异均无统计学意义(均P>0.05)。门类水平的微生物组β多样性分析显示两组之间的菌群组成无明显差异(P=0.076)。属类水平上β多样性分析结果显示,两组间差异大于两组内差异(P=0.04),通过菌属丰度之间的比较,发现粪球菌属的菌群丰度可能会促进MLH1蛋白缺失(校正后的P<0.01)。然而,无论各临床病理参数或是不同丰度的关键物种之间,Shannon指数均无明显差异(均P>0.05)。结论:近端SCC患者MLH1蛋白表型与肠道菌群的组成和多样性密切相关。此外,鉴定出粪球菌属可能成为该人群MLH1蛋白表达缺失的关键物种,并为今后该病的研究与防治提供新的切入点。Background and Aims:Mutations in the mutL homolog 1 (MLH1) gene can lead to inactivation of the DNA mismatch repair (MMR) system,increasing the risk of colorectal cancer.Additionally,growing evidence suggests that alterations in the composition and function of the intestinal microbiota are closely associated with the occurrence and development of colorectal cancer.However,the relationship between MLH1 protein expression and the intestinal microbiota remains unclear.Therefore,this study aimed to explore the potential relationship between them by analyzing the differences in the microbial composition of tumor tissues between patients with proximal sporadic colon cancer (SCC) and different MLH1 protein phenotypes in Northeast China.Methods:Tumor tissue samples and clinical data were collected from 407 patients with proximal SCC treated in Harbin First Hospital and Heilongjiang Provincial Hospital between 2020 and 2021.Immunohistochemistry was used to screen for cases with MLH1 protein deficiency (deficiency group)and intact MLH1 protein (control group).Microbial DNA extracted from the intestinal tumor tissues was analyzed using 16S rRNA gene sequencing technology for bioinformatics analysis.The relationship between clinicopathologic features and the diversity of specific taxa and microbial diversity was analyzed.Results:A total of 20 cases were screened in the deficiency group,and 18 cases were screened in the control group.Preliminary analysis of clinical data showed that the larger the tumor,the higher the risk of MLH1 protein deficiency (P<0.05).The α-diversity of the microbial community within tumor tissues under different MLH1 statuses showed no statistically significant differences except for the Shannon index (P=0.042).Other diversity indices had no significant difference (all P>0.05).The β-diversity analysis of microbial communities at the phylum level showed no significant differences between the two groups (P=0.076).At the genus level,β-diversity analysis showed that the differences between the two grou

关 键 词：结肠肿瘤 DNA错配修复 MutL同源蛋白1 微生物群 

分 类 号：R735.3[医药卫生—肿瘤]