Tanca Alessandro, Abbondio Marcello, Fiorito Giovanni, Pira Giovanna, Sau Rosangela, Manca Alessandra, Muroni Maria Rosaria, Porcu Alberto, Scanu Antonio Mario, Cossu-Rocca Paolo, De Miglio Maria Rosaria, Uzzau Sergio
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Medical Research Council (MRC), Centre for Environment and Health, Imperial College London, London, United Kingdom.
Front Microbiol. 2022 Apr 14;13:869523. doi: 10.3389/fmicb.2022.869523. eCollection 2022.
Recent studies have provided evidence of interactions among the gut microbiota (GM), local host immune cells, and intestinal tissues in colon carcinogenesis. However, little is known regarding the functions exerted by the GM in colon cancer (CC), particularly with respect to tumor clinical classification and lymphocyte infiltration. In addition, stool, usually employed as a proxy of the GM, cannot fully represent the original complexity of CC microenvironment. Here, we present a pilot study aimed at characterizing the metaproteome of CC-associated colonic luminal contents and identifying its possible associations with CC clinicopathological features. Colonic luminal contents were collected from 24 CC tissue specimens immediately after surgery. Samples were analyzed by shotgun metaproteomics. Almost 30,000 microbial peptides were quantified in the samples, enabling the achievement of the taxonomic and functional profile of the tumor-associated colonic luminal metaproteome. Upon sample aggregation based on tumor stage, grade, or tumor-infiltrating lymphocytes (TILs), peptide sets enabling discrimination of sample groups were identified through discriminant analysis (DA). As a result, and were significantly enriched in high-stage and high-grade CC, respectively. Among metabolic functions, formate-tetrahydrofolate ligase was significantly associated with high-stage CC. Finally, based on the results of this pilot study, we assessed the optimal sample size for differential metaproteomic studies analyzing colonic luminal contents. In conclusion, we provide a detailed picture of the microbial and host components of the colonic luminal proteome and propose promising associations between GM taxonomic/functional features and CC clinicopathological features. Future studies will be needed to verify the prognostic value of these data and to fully exploit the potential of metaproteomics in enhancing our knowledge concerning CC progression.
最近的研究提供了肠道微生物群（GM）、局部宿主免疫细胞和肠道组织在结肠癌发生过程中相互作用的证据。然而，关于GM在结肠癌（CC）中发挥的功能，尤其是与肿瘤临床分类和淋巴细胞浸润方面，我们所知甚少。此外，通常用作GM替代物的粪便，无法完全代表CC微环境的原始复杂性。在此，我们开展了一项初步研究，旨在表征与CC相关的结肠腔内容物的元蛋白质组，并确定其与CC临床病理特征的可能关联。手术结束后立即从24个CC组织标本中收集结肠腔内容物。通过鸟枪法元蛋白质组学对样本进行分析。样本中定量了近30,000种微生物肽，从而实现了肿瘤相关结肠腔元蛋白质组的分类学和功能概况。根据肿瘤分期、分级或肿瘤浸润淋巴细胞（TILs）对样本进行汇总后，通过判别分析（DA）鉴定出能够区分样本组的肽集。结果，[具体物质1]和[具体物质2]分别在高分期和高分级CC中显著富集。在代谢功能中，甲酸 - 四氢叶酸连接酶与高分期CC显著相关。最后，基于这项初步研究的结果，我们评估了分析结肠腔内容物的差异元蛋白质组学研究的最佳样本量。总之，我们提供了结肠腔蛋白质组中微生物和宿主成分的详细情况，并提出了GM分类学/功能特征与CC临床病理特征之间有前景的关联。未来需要进一步研究来验证这些数据的预后价值，并充分利用元蛋白质组学的潜力来增进我们对CC进展的了解。
