Gut Microbiome-Associated SNPs and Their Impact on the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: A Mendelian Randomization Study

Various studies and trials have indicated a potential link between cancer and the microbiome of the digestive system. Nevertheless, there is insufficient research on the connection between the gut microbiome and Head and Neck Squamous Cell Carcinoma (HNSCC). Genetic differences in the intestinal microbiome were obtained from the MiBioGen repository. We recognized gut microbiota across various taxonomic levels including phylum, class, order, family, and genus. UK Biobank provided the HNSCC data, while the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database (GSE181919) supplied the HNSCC-related data for single-cell correlation analysis. Following this, we performed Mendelian Randomization (MR), analyzed immune cell infiltration, conducted Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA), examined regulatory networks of important genes, conducted single-cell analysis, and performed statistical analysis. Seven ideal causal connections were discovered between the gut microbiome and HNSCC, with their validity confirmed by analyzing heterogeneity and genetic diversity. Examination showed that the Single-nucleotide polymorphism(SNP) genes have a strong connection to levels of immune cell infiltration and are important in shaping the immune microenvironment (IME) . Additional research revealed distinct signaling pathways and transcriptional regulatory networks that were enhanced by the seven SNP genes. Through the use of MR, we were able to establish a direct connection between the gut microbiome and HNSCC. This may contribute to providing new insights into the mechanisms and clinical research of gut microbiota-mediated HNSCC.

诸多研究与试验均证实，消化系统微生物组与癌症之间存在潜在关联。然而，目前针对肠道微生物组与头颈部鳞状细胞癌（Head and Neck Squamous Cell Carcinoma, HNSCC）之间关联的研究仍较为匮乏。肠道微生物组的遗传差异数据取自MiBioGen资源库。我们在门、纲、目、科、属等多个分类学层级上完成了肠道菌群的识别与注释。英国生物银行（UK Biobank）提供了HNSCC相关数据，而美国国家生物技术信息中心基因表达综合数据库（National Center for Biotechnology Information Gene Expression Omnibus, NCBI GEO）的GSE181919数据集则为单细胞相关性分析提供了HNSCC相关数据。随后，我们开展了孟德尔随机化（Mendelian Randomization, MR）分析、免疫细胞浸润分析、基因集变异分析（Gene Set Variation Analysis, GSVA）与基因集富集分析（Gene Set Enrichment Analysis, GSEA），解析了关键基因的调控网络，完成了单细胞分析与统计学检验。本研究共发现7条肠道微生物组与HNSCC之间的因果关联，并通过异质性与遗传多样性分析验证了其有效性。分析表明，单核苷酸多态性（Single-nucleotide polymorphism, SNP）基因与免疫细胞浸润水平密切相关，在免疫微环境（immune microenvironment, IME）的塑造中发挥着重要作用。进一步研究显示，上述7个SNP基因可增强特定信号通路与转录调控网络的活性。本研究通过孟德尔随机化分析明确了肠道微生物组与HNSCC之间的直接关联，可为肠道菌群介导的HNSCC发病机制研究与临床转化提供全新的视角。

搜集汇总

背景与挑战

背景概述

该数据集通过孟德尔随机化方法，研究了肠道微生物组相关遗传变异（SNPs）与头颈鳞状细胞癌免疫微环境之间的因果关联。分析结合了多组学数据（如单细胞RNA测序和免疫浸润分析），发现了七个关键SNP基因，这些基因显著影响免疫细胞浸润并参与调控肿瘤免疫微环境。数据集为理解肠道微生物介导的头颈癌机制提供了新的见解，并支持相关临床研究探索。