Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Wilrijk, Belgium.
Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium.
Microbiome. 2023 Apr 21;11(1):86. doi: 10.1186/s40168-023-01534-w.
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.
我们旨在确定在胃腺癌中塑造肿瘤微环境和临床结局的粘蛋白-微生物群特征。
我们使用经过验证的基于粘蛋白的 RT-qPCR 对 108 例胃腺癌和 20 例功能性消化不良病例中的粘蛋白表型进行高通量分析，随后进行免疫组织化学验证，并将数据与临床结局参数相关联。通过 16S rRNA 基因测序评估胃微生物群，确定分类群和群落组成，分析微生物网络，并与粘蛋白表型和表达相关联推断宏基因组。
具有肠粘蛋白环境或高水平 MUC13 表达的胃腺癌与生存率差相关。相反，胃 MUC5AC 或 MUC6 丰度与更有利的结局相关。口腔分类群 Neisseria、Prevotella 和 Veillonella 在具有肠型和混合表型的肿瘤中具有中心性，并且与 MUC13 过表达相关，突出了它们在 GC 中 MUC13 信号传导中的潜在驱动作用。此外，在肠型和混合粘蛋白表型肿瘤中观察到密集的细菌网络，而在无粘蛋白表型肿瘤中观察到最低的群落复杂性，这是由于幽门螺杆菌丰度较高导致多样性降低。口腔或肠道微生物的富集依赖于粘蛋白表型。更具体地说，肠粘蛋白表型肿瘤有利于形成强共现网络的促炎口腔分类群的建立。
我们的研究结果强调了粘蛋白在胃癌预后中的关键作用，并在肿瘤微环境中塑造微生物网络。具体来说，与异常 MUC13 表达相关的丰富口腔分类群可以成为预测疾病结局的潜在生物标志物。
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