肝胆胰外科杂志2025，Vol.37Issue(6)：402-410,9.DOI:10.11952/j.issn.1007-1954.2025.06.008
胰腺导管腺癌微生物亚型分析揭示肿瘤微环境异质性
Intratumoral microbial subtyping in pancreatic ductal adenocarcinoma reveals tumor microenvironment heterogeneity
摘要
Abstract
Objective To explore the microbial subtypes of pancreatic ductal adenocarcinoma(PDAC)and their interactions with the host genome and tumor microenvironment.Methods PDAC transcriptome data from the GEO database and PDAC metagenome data from the BioProject database were integrated,and PDAC tumor microbial subtypes were determined by nonnegative matrix factorization(NMF)clustering.Differential analysis was performed between the microbiome and transcriptome of each PDAC subtype.Combined with the differential analysis,survival analysis was used to determine the dominant microorganisms of each subtype with prognostic significance.Immune infiltration analysis was used to compare the tumor microenvironment of each subtype.Weighted gene co-expression network analysis(WGCNA)was applied to analyze the microbe-genome interaction in the co-expression network.Results PDAC microorganisms could be divided into three subtypes:C1(dominated by Weeksellaceae),C2(dominated by Sphingomonadaceae),and C3(dominated by Pseudomonadaceae).The C3 subtype had the highest alpha diversity and relatively poor prognosis of patients among all subtypes.In the C3 subtype,the antibacterial pathway was abnormally activated,and the tumor microenvironment showed immunosuppressive characteristics.WGCNA revealed the most significant interaction between the genus Brevundimonas and the tumor genome,involving pathways such as oxidative metabolism and PI3K/AKT.Conclusion The heterogeneity of each subtype of PDAC microorganisms affects tumor progression by regulating the host genome and immune microenvironment.The high diversity and poor prognostic characteristics of the C3 subtype suggest its value as a potential therapeutic target.关键词
胰腺导管腺癌/肿瘤微生物/肿瘤微环境/宿主-微生物互作/非负矩阵分解/加权基因共表达网络分析Key words
pancreatic ductal adenocarcinoma/tumor microbiome/tumor microenvironment/host-microbe interactions/non-negative matrix factorization/weighted gene co-expression network analysis分类
临床医学引用本文复制引用
麻忠武,彭明晖,林泉,管时伟,张凯伦,俞海波..胰腺导管腺癌微生物亚型分析揭示肿瘤微环境异质性[J].肝胆胰外科杂志,2025,37(6):402-410,9.基金项目
浙江省医药卫生科技计划(2025KY1506) （2025KY1506）
浙江省自然科学联合基金(KLY25H160064). （KLY25H160064）
