我们的目标是确定黏液-微生物群落特征对胃腺癌肿瘤微环境和临床结果的影响。我们使用经过验证的基于黏液的RT-qPCR技术对108例胃腺癌和20例功能性消化不良症状进行高通量黏液表型分析，并进行免疫组织化学验证，并将数据与临床结果参数进行相关性分析。通过16S rRNA基因测序评估胃微生物群落，确定分类和社区组成，分析微生物网络，并与黏液表型和表达相关的元基因组进行推断。具有肠道型黏液环境或高水平MUC13表达的胃腺癌与不良生存率相关。相反，胃MUC5AC或MUC6的丰度与更有利的结果相关。口腔菌群Neisseria、Prevotella和Veillonella在具有肠和混合黏液表型的肿瘤中具有中心性，并与MUC13过度表达相关，突出了它们在GC中潜在驱动因子的作用。此外，在肠和混合黏液表型肿瘤中观察到密集的细菌网络，而由于较高的幽门螺杆菌丰度导致更低的多样性，在null黏液表型肿瘤中显示了最低的社区复杂性。口腔或肠道微生物的富集取决于黏液表型。更具体地说，肠道黏液表型肿瘤有利于建立形成强大共存网络的促炎性口腔菌群。我们的结果强调了黏液在胃癌预后和微生物网络塑造中的关键作用。特别是与异常MUC13表达相关的富集口腔菌群可以作为预测疾病结果的潜在生物标志物。视频摘要。©2023作者。

We aimed to identify mucin-microbiome signatures shaping the tumor microenvironment in gastric adenocarcinomas and clinical outcomes.We performed high-throughput profiling of the mucin phenotypes present in 108 gastric adenocarcinomas and 20 functional dyspepsia cases using validated mucin-based RT-qPCRs with subsequent immunohistochemistry validation and correlated the data with clinical outcome parameters. The gastric microbiota was assessed by 16S rRNA gene sequencing, taxonomy, and community composition determined, microbial networks analyzed, and the metagenome inferred in association with mucin phenotypes and expression.Gastric adenocarcinomas with an intestinal mucin environment or high-level MUC13 expression are associated with poor survival. On the contrary, gastric MUC5AC or MUC6 abundance was associated with a more favorable outcome. The oral taxa Neisseria, Prevotella, and Veillonella had centralities in tumors with intestinal and mixed phenotypes and were associated with MUC13 overexpression, highlighting their role as potential drivers in MUC13 signaling in GC. Furthermore, dense bacterial networks were observed in intestinal and mixed mucin phenotype tumors whereas the lowest community complexity was shown in null mucin phenotype tumors due to higher Helicobacter abundance resulting in a more decreased diversity. Enrichment of oral or intestinal microbes was mucin phenotype dependent. More specifically, intestinal mucin phenotype tumors favored the establishment of pro-inflammatory oral taxa forming strong co-occurrence networks.Our results emphasize key roles for mucins in gastric cancer prognosis and shaping microbial networks in the tumor microenvironment. Specifically, the enriched oral taxa associated with aberrant MUC13 expression can be potential biomarkers in predicting disease outcomes. Video Abstract.© 2023. The Author(s).