结直肠癌肝转移和非肝转移患者的肠道菌群构成差异  

Composition diff erences of intestinal flora between colorectal cancer patients with and without liver metastasis

作　　者：樊启林 张松 徐丹 文峰 朱杰伦 张俊 金敏 师琳丽 周彬[2] 程明霞 程建国 刘红利[2] Fan Qilin;Zhang Song;Xu Dan;Wen Feng;Zhu Jielun;Zhang Jun;Jin Min;Shi Linli;Zhou Bin;Cheng Mingxia;Cheng Jianguo;Liu Hongli(Department of Gastroenterology,General Hospital of Central Theater Command,Wuhan 430070,China;Department of Abdominal Oncology,Cancer Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]中部战区总医院消化内科,湖北武汉430070 [2]华中科技大学同济医学院附属协和医院肿瘤中心腹部肿瘤科,湖北武汉430022

出　　处：《实用肿瘤杂志》2023年第3期229-238,共10页Journal of Practical Oncology

基　　金：国家重点研发计划(2018YFC1313300)。

摘　　要：目的分析结直肠癌伴肝转移(liver metastasis,LM)和结直肠癌不伴肝转移(non-liver metastasis,NLM)患者的肠道微生物特征。方法选取2015年1月1日至2017年12月31日华中科技大学同济医学院附属协和医院的结直肠癌患者73例作临床研究。建立2个队列,分别是原发肿瘤组织固定及石蜡包埋样本队列(primary tumor tissues with fixation and paraffin embedding,FFPE samples)和粪便标本队列(Fecal samples)。每个队列按照有无LM分为两组:LM组和NLM组。FFPE samples队列中,LM组入组15例,NLM组入组30例;Fecal samples队列中,LM组入组12例,NLM组入组16例。采用16S rRNA高通量测序分析LM组和NLM组患者肠道菌群的多样性和物种组成情况。采用随机森林模型进一步寻找可预测结直肠癌LM的潜在微生物标志物。结果在2个队列中,LM组肠道微生物丰富度和多样性均高于NLM组(均P<0.05),LM组和NLM组的物种组成差异均具有统计学意义(均P<0.05)。拟杆菌门在2个队列的LM组中均显著富集。随机森林模型分析进一步表明,拟杆菌门可作为预测结直肠癌LM的潜在微生物标志物,对评估其无进展生存率及总生存率等预后生存状态具有重要意义。结论结直肠癌LM组和NLM组之间具有不同的肠道菌群特征。拟杆菌门对结直肠癌LM和预后不良具有潜在的预测价值。Objective To analyze the intestinal microbiota characteristics of colorectal cancer patients with liver metastasis(LM)and with non-liver metastasis(NLM).Methods A total of 73 colorectal cancer patients were enrolled from January 1,2015 to December 31,2017 in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology.Two cohorts were established,FFPE samples(primary tumor tissues with fixation and paraffin embedding)and Fecal samples.Each cohort was divided into two groups according to the presence or absence of LM:LM group and NLM group.In the FFPE samples cohort,15 cases were included in the LM group and 30 cases in the NLM group.In the Fecal samples cohort,12 cases were enrolled in the LM group and 16 cases were enrolled in the NLM group.16S rRNA high-throughput sequencing was used to analyze the diversity and species composition of intestinal flora in the LM and NLM groups.Furthermore,the stochastic forest model was used to further search for potential microbial markers for predicting LM of colorectal cancer.Results The gut microbial richness and diversity were higher in the LM group than in the NLM group in both cohorts(all P<0.05).Further,there was significant difference in species composition between the LM and NLM groups in both cohorts(both P<0.05).Phylum Bacteroidetes presented consistent and significant enrichment in the LM group in both cohorts.Furthermore,the stochastic forest model analysis indicated that Bacteroidetes could be used as a potential microbial marker for predicting LM of colorectal cancer,which was of great significance for evaluating progression-free survival and overall survival.Conclusions There are different gut microbiota character-istics between the LM and NLM groups.Bacteroidetes has potential predictive value for LM and poor prognosis of colorectal cancer.

关 键 词：结直肠癌 肠道菌群 肝转移 拟杆菌门 

分 类 号：R735.34[医药卫生—肿瘤]