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食管鳞癌患者和健康人口腔菌群的比较和意义

Oral Microbiome Differences Between ESCC Patients and Healthy Controls:Significance and Implications
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摘要 目的基于中国食管癌高发区人群,通过比较食管鳞癌(esophageal squamous cell carcinoma,ESCC)患者和健康对照者口腔菌群分布特征和构成差异,鉴定ESCC相关的特异性口腔菌群标志物,为筛选早期诊断和早期筛查ESCC的菌群标志物奠定基础。方法收集安阳市肿瘤医院经病理学确诊的48例原发性ESCC患者和50例经性别、年龄匹配的健康对照的口腔拭子样本,进行V3~V4区域16S rRNA基因测序,采用Wilcoxon秩和检验比较两组菌群Alpha多样性及相对丰度差异,采用线性判别分析(linear discriminant analysis effect size,LEfSe)筛选差异性物种,ROC曲线分析菌群预测ESCC的价值。结果ESCC患者菌群多样性低于健康对照组(P<0.05),且两组人群的菌群整体构成不同(P=0.001)。厚壁菌门、变形菌门、拟杆菌门、放线菌门和梭杆菌门是两组常见门类。相比于健康对照组,ESCC组厚壁菌门和梭杆菌门相对丰度升高,而变形菌门和放线菌门丰度减少(均P<0.05);ESCC组链球菌属、梭杆菌属、拟普雷沃氏菌属和纤毛菌属等属的丰度显著提升,而奈瑟菌属、二氧化碳噬纤维菌属等属的丰度下降(均P<0.05)。特别重要的是,牙龈卟啉单胞菌、牙髓卟啉单胞菌、坦纳拟普雷沃菌、南锡普雷沃菌等菌种在ESCC组富集;联合南锡普雷沃菌、坦纳拟普雷沃菌和牙龈卟啉单胞菌区分ESCC与健康个体(AUC=0.728,特异度0.760,灵敏度0.646)的效果优于任一单个菌种。结论牙龈卟啉单胞菌、坦纳拟普雷沃菌、南锡普雷沃菌和牙髓卟啉单胞菌是初步筛查ESCC患者的菌群标志物,且联合前三个菌种有区分ESCC与健康个体的良好效能。 Objective To identify specific oral microbial biomarkers for esophageal squamous cell carcinoma(ESCC)by comparing the distribution and composition of oral microbiota between ESCC patients and healthy controls in a high-risk Chinese population,thereby laying the foundation for developing microbial-based early diagnostic and screening methods for ESCC.Methods Oral swab samples from 48 patients with primary ESCC diagnosed pathologically and 50 healthy controls matched by sex and age were collected from Anyang Cancer Hospital.The V3-V4 region of 16S rRNA gene was sequenced.Wilcoxon rank sum test was used to compare Alpha diversity and relative abundance differences of oral microbiota between the two groups.Linear discriminant analysis Effect Size(LEfSe)was used to identify differentially abundant taxa,and ROC curve was usedto analyze the value of oral microbiota in predicting ESCC.Results The Alpha diversity of ESCC decreased compared with healthy control group(P<0.05),and the two groups had different community composition(P=0.001).The main phyla were Firmicutes,Proteobacteria,Bacteroidota,Actinobacteriota and Fusobacteriota in both groups.Compared with the healthy control group,the relative abundances of Firmicutes and Fusobacteriota were increased,and those of Proteobacteria and Actinobacteria were decreased in ESCC group(all P<0.O5).At the genus level,the abundance of Streptococcus,Fusobacterium,Alloprevotella and Leptotrichia in ESCC group was significantly higher,and that of Neisseria and Ca pnocytophaga was lower(all P<0.05).Notably,Porphyromonas gingivalis,Porphyromonas endodontalis,Alloprevotella tannerae,and Prevotella nanceiensis were significantly enriched in ESCC patients.A combination of P.nanceiensis,A.tannerae,and P.gingivalis demonstrated better discriminatory power(AUC=0.728,specificity 0.760,sensitivity 0.646)than any single species alone.Conclusion P.gingivalis,A.tannerae,P.nanceiensis,and P.endodontalis may serve as potential biomarkers for preliminary ESCC screening.The combination of the first three species exhibits promising performance in distinguishing ESCC patients from healthy individuals.
作者 孔金玉 刘怡文 王健 孙蔚 钱梦凡 李若楠 高社干 Kong Jinyu;Liu Yiwen;Wang Jian(Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment,The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Luoyang 471023,China;Department of Image Center,the First Affiliated Hospital,and College of Clinical Medicine of Henan University of Science and Technology,Luoyang 471023,China)
出处 《华中科技大学学报(医学版)》 北大核心 2025年第6期842-851,共10页 Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金 国家自然科学基金资助项目(No.81972571) 河南科技大学第一附属医院肿瘤学国家临床重点专科建设开放联合基金科技攻关项目(No.ZLKFJJ20230504) 河南省医学科技攻关计划项目(No.LHGJ20250560)。
关键词 食管鳞状细胞癌 口腔菌群 16S rRNA基因测序 esophageal squamous cell carcinoma oral microbiota l6S rRNA gene sequencing
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