基于宏基因组学分析结直肠癌患者化疗耐药与肠道菌群的关系  

Analysis of the relationship between chemoresistance and gut microbiota in colorectal cancer patients based on metagenomics

作　　者：佘玉奇 林盛 朱志伟[1] 方翎[1] SHE Yuqi;LIN Sheng;ZHU Zhiwei;FANG Ling(Department of Pharmacy,Cancer Hospital Affiliated to Shantou University Medical School,Shantou 505041,China)

机构地区：[1]汕头大学医学院附属肿瘤医院药学部,广东汕头505041

出　　处：《胃肠病学和肝病学杂志》2024年第9期1160-1166,共7页Chinese Journal of Gastroenterology and Hepatology

基　　金：广东省医学科学技术研究基金项目(A2022452);广东省基础与应用基础研究基金(2022A1515220076)。

摘　　要：目的基于宏基因组学分析结直肠癌患者化疗耐药与肠道菌群的关系。方法选取2021年9月至2023年3月入院就诊的150例结直肠癌患者为研究对象,另选取150名健康者为健康组。根据结直肠癌组患者化疗敏感情况将150例患者分为敏感组(n=82)和不敏感组(n=68),通过宏基因组测序,分析两组的OTU菌群丰度、α-多样性、β-多样性、差异性菌种、差异性耐药基因。通过相关性分析判断肠道菌群变化与耐药基因之间的相关性。结果结直肠癌组的OTU菌群丰度、α-多样性、β-多样性均低于健康组。不敏感组的OTU菌群丰度、α-多样性、β-多样性均低于敏感组。结直肠癌组与健康组之间共有24个差异性菌种,其中6个菌种在结直肠癌患者肠道中显著富集,18个菌种在结直肠癌组中显著降低;不敏感组与健康组相比,6个菌种明显富集。结直肠癌组和健康组在13种耐药基因间存在显著性差异,且全部在结直肠癌组肠道中富集,不敏感组肠道中13种耐药基因富集显著高于敏感组。对结直肠癌组和健康组的差异性肠道菌种与耐药基因进行相关性分析,6个差异性菌种分别与13种耐药基因呈正相关。结论结直肠癌患者肠道菌群丰度明显降低,部分菌群与化疗敏感性存在密切关系,与耐药基因呈显著正相关。Objective To investigate the relationship between chemoresistance and gut microbiota in colorectal cancer patients based on metagenomics.Methods A total of 150 colorectal cancer patients admitted to the hospital from Sep.2021 to Mar.2023 were selected as the research subjects,and another 150 healthy individuals were selected as the healthy group.According to the chemotherapy sensitivity of colorectal cancer patients,150 patients were divided into a sensitive group(n=82)and an insensitive group(n=68).The abundance of OTU microbiota,α-diversity,β-diversity,differential strains and differential resistance genes in both groups were analyzed through metagenomic sequencing.The correlation between the changes of gut microbiota and drug resistance genes was determined by correlation analysis.Results The abundance of OTU microbiota,α-diversity,β-diversity in the colorectal cancer group was lower than that of the healthy group.The abundance of OTU microbiota,α-diversity,β-diversity in the insensitive group was lower than that of the sensitive group.There were a total of 24 differential bacterial strains between the colorectal cancer group and the healthy group,of which 6 strains were significantly enriched in the intestines of colorectal cancer patients,and 18 strains were significantly reduced in the colorectal cancer group.Compared with the healthy group,the insensitive group showed a significant enrichment of 6 bacterial strains.There was a significant difference between the colorectal cancer group and healthy group in the 13 drug resistance genes,and all of them were enriched in the intestine of the colorectal cancer group.The enrichment of 13 drug resistance genes in the intestine of the insensitive group was significantly higher than that of the sensitive group.A correlation analysis was conducted between differential gut microbiota and drug resistance genes in the colorectal cancer group and the healthy group.Six differential bacterial strains were positively correlated with 13 drug resistance genes,respective

关 键 词：结直肠癌 化疗耐药 肠道菌群 影响因素 

分 类 号：R735.3[医药卫生—肿瘤]