基于多肿瘤标志物表达的肝癌患者肠道微生物组特征分析  

Analysis of intestinal microbiome characteristics in patients with liver cancer based on the expression of multiple tumor markers

作　　者：吕振选 吕朝凤 田国防 李春青 LV Zhenxuan;LV Chaofeng;TIAN Guofang(l.Xinxiang Central Hospital/Department of Oncology,Fourth Clinical College,Xinxiang Medical College,Xinxiang 2022300,Henan,China;Xinxiang Central Hospital/Health Management Department of the Fourth Clinical College of Xinxiang Medical College,Xinxiang 2022300,Henan,China)

机构地区：[1]新乡市中心医院/新乡医学院第四临床学院肿瘤内科,河南新乡2022300 [2]新乡市中心医院/新乡医学院第四临床学院健康管理部,河南新乡2022300

出　　处：《中国病原生物学杂志》2025年第4期421-427,433,共8页Journal of Pathogen Biology

基　　金：河南省医学科技攻关计划项目(LHGJ20210919)。

摘　　要：目的探讨肝细胞癌患者的肠道微生物组特征,分析其与多种肿瘤标志物水平的关联性,为肝细胞癌的早期诊断和治疗提供临床思路。方法收集2023年10月至2024年10月于医院就诊的60例肝细胞癌患者(病例组)和60例健康志愿者(对照组)的粪便和血清样本。采用16SrRNA基因测序技术分析肠道微生物组组成,检测血清中甲胎蛋白(AFP)、AFP-L3、异常凝血酶原(DCP)、糖蛋白3(GPC3)和TF(TF)水平。比较2组间菌群多样性和组成差异,应用Spearman相关分析和多元线性回归模型评估菌群与肿瘤标志物间的关联。结果与对照组相比,病例组肠道菌群的Chao1指数显著降低(320.45±35.28vs350.62±30.15,P<0.001),Shannon指数显著降低(3.85±0.42vs4.20±0.38,P<0.001),Simpson指数也显著降低(0.918±0.025vs0.940±0.022,P<0.001)。在属水平上,病例组致病菌属大肠埃希菌属(12.5%±2.2%vs4.0%±1.0%,P<0.001)、肠杆菌属(5.8%±1.5%vs2.0%±0.8%,P<0.001)相对丰度显著升高,益生菌属拟杆菌属(18.0%±3.5%vs22.5%±4.0%,P<0.001)、毛螺菌属(3.2%±1.0%vs6.5%±1.5%,P<0.001)显著降低。Spearman相关分析显示,AFP水平与大肠埃希菌属相对丰度呈正相关(ρ=0.582,P<0.001),与拟杆菌属呈负相关(ρ=-0.568,P<0.001)。多元线性回归分析表明,大肠埃希菌属增加与AFP升高独立相关(β=0.425,P<0.001)。结论肝细胞癌患者的肠道微生物组多样性降低,菌群组成显著改变,致病菌增多、益生菌减少。肿瘤标志物水平与特定菌属的丰度密切相关。肠道菌群失调可能在肝细胞癌的发生发展中发挥重要作用,调节肠道微生态或可成为肝细胞癌防治的新策略。Objective To explore the characteristics of the intestinal microbiome in patients with hepatocellular carcinoma,analyze its correlation with the levels of multiple tumor markers,and provide clinical ideas for the early diagnosis and treatment of hepatocellular carcinoma.Methods Fecal and serum samples of 6o hepatocellular carcinoma patients(case group)and 60 healthy volunteers(control group)who visited the hospital from October 2023 to October 2024 were collected.16S rRNA gene sequencing technology was used to analyze the composition of the intestinal microbiome,and serum alpha-fetoprotein(AFP),AFP-L3,abnormal prothrombin(DCP),glycoprotein 3(GPC3)and TF(TF)levels were detected.The diversity and composition of the bacterial flora between the two groups were compared,and Spearman correlation analysis and multiple linear regression models were used to evaluate the association between the bacterial flora and tumor markers.Results Compared with the control group,the Chaol index of the intestinal flora in the case group was significantly lower(320.45±35.28 vs 350.62±30.15,P<0.001),and the Shannon index was significantly lower(3.85±0.42 vs 4.20±0.38,P<0.001),Simpson index was also significantly reduced(0.918±0.025 vs 0.940±0.022,P<0.001).At the genus level,the pathogenic bacteria in the case group were Escherichia coli(12.5%±2.2%vs 4.0%±1.0%,P<0.001),Enterobacter(5.8%±1.5%vs 2.0%±0.8%,P<0.001)the relative abundance increased significantly,the probiotic genera Bacteroidetes(18.0%±3.5%vs 22.5%±4.0%,P<0.001),Lachnospira(3.2%±1.0%vs 6.5%±1.5%,P<0.001)was significantly reduced.Spearman correlation analysis showed that AFP levels were positively correlated with the relative abundance of Escherichia coli(ρ=0.582,P<0.001)and negatively correlated with Bacteroidetes(ρ=-0.568,P<0.001).Multiple linear regression analysis showed that the increase in Escherichia coli was independently related to the increase in AFP(β=0.425,P<0.001).Conclusion The diversity of the intestinal microbiome of patients with hepatocellular

关 键 词：肝细胞癌 肠道微生物组 肿瘤标志物 菌群多样性 相关性分析 

分 类 号：R73[医药卫生—肿瘤]