Department of Cancer Immunology, Genentech, Inc., South San Francisco, CA, USA.
Department of OMNI Bioinformatics, Genentech, Inc., South San Francisco, CA, USA.
Cell Rep Med. 2023 Feb 21;4(2):100920. doi: 10.1016/j.xcrm.2023.100920. Epub 2023 Jan 26.
While the association between colorectal cancer (CRC) features and Fusobacterium has been extensively studied, less is known of other intratumoral bacteria. Here, we leverage whole transcriptomes from 807 CRC samples to dually characterize tumor gene expression and 74 intratumoral bacteria. Seventeen of these species, including 4 Fusobacterium spp., are classified as orally derived and are enriched among right-sided, microsatellite instability-high (MSI-H), and BRAF-mutant tumors. Across consensus molecular subtypes (CMSs), integration of Fusobacterium animalis (Fa) presence and tumor expression reveals that Fa has the most significant associations in mesenchymal CMS4 tumors despite a lower prevalence than in immune CMS1. Within CMS4, the prevalence of Fa is uniquely associated with collagen- and immune-related pathways. Additional Fa pangenome analysis reveals that stress response genes and the adhesion FadA are commonly expressed intratumorally. Overall, this study identifies oral-derived bacteria as enriched in inflamed tumors, and the associations of bacteria and tumor expression are context and species specific.
虽然结直肠癌（CRC）特征与梭杆菌之间的关联已被广泛研究，但对其他肿瘤内细菌知之甚少。在这里，我们利用来自 807 个 CRC 样本的全转录组数据，双重表征肿瘤基因表达和 74 种肿瘤内细菌。其中 17 种细菌，包括 4 种梭杆菌属，被归类为口腔来源，并且在右侧、微卫星不稳定高（MSI-H）和 BRAF 突变型肿瘤中富集。在共识分子亚型（CMS）中，整合 Fusobacterium animalis（Fa）的存在和肿瘤表达表明，尽管 Fa 的患病率低于免疫 CMS1，但在间充质 CMS4 肿瘤中，Fa 具有最显著的关联。在 CMS4 中，Fa 的患病率与胶原和免疫相关途径具有独特的相关性。Fa 的附加泛基因组分析表明，应激反应基因和粘附 FadA 通常在肿瘤内表达。总体而言，这项研究确定了口腔来源的细菌在炎症性肿瘤中富集，并且细菌和肿瘤表达的关联具有特定的上下文和物种特异性。
