Background/Objectives: The role of the gut microbiome in cancer biology has become an increasingly prominent area of research, particularly regarding the role of microbial metabolites and their receptors (MMRs). These metabolites, through the various gut–organ axes, have been proven to influence several pathogenetic mechanisms. This study conducted a comprehensive pan-cancer analysis of MMR transcriptomic profiles across twenty-three cancer types, exploring the mechanisms through which they can influence cancer development and progression. Methods: Utilizing both cancer cell lines from CCLE (Cancer Cell Line Encyclopedia) and human tumor samples from TCGA (The Cancer Gene Atlas), we analyzed 107 MMRs interacting with microbial metabolites such as short-chain fatty acids, bile acids, indole derivatives, and others while studying their interactions with key known cancer genes. Results: Our results revealed that certain MMRs, such asGPR84and serotonin receptors, are consistently upregulated in various malignancies, while others, likeADRA1A, are frequently downregulated, suggesting diverse roles in cancer pathophysiology. Furthermore, we identified significant correlations between MMR expression and cancer hallmark genes and pathways, including immune evasion, proliferation, and metastasis. Conclusions: These findings suggest that the interactions between microbial metabolites and MMRs may serve as potential biomarkers for cancer diagnosis, prognosis, and therapy, highlighting their therapeutic potential. This study underscores the significance of the microbiota–cancer axis and provides novel insights into microbiome-based strategies for cancer treatment.
背景/目的：肠道微生物组在癌症生物学中的作用已成为日益重要的研究领域，尤其关注微生物代谢物及其受体（MMRs）的功能。这些代谢物通过多种肠-器官轴已被证实能影响多种致病机制。本研究对23种癌症类型中的MMR转录组谱进行了全面的泛癌分析，探讨其影响癌症发生发展的作用机制。方法：通过整合CCLE（癌细胞系百科全书）的癌细胞系数据与TCGA（癌症基因组图谱）的人类肿瘤样本数据，我们分析了107种与短链脂肪酸、胆汁酸、吲哚衍生物等微生物代谢物相互作用的MMRs，并研究其与关键已知癌症基因的相互作用网络。结果：研究发现某些MMRs（如GPR84和血清素受体）在多种恶性肿瘤中持续上调，而其他受体（如ADRA1A）则频繁下调，提示其在癌症病理生理过程中具有多样化作用。此外，我们发现了MMR表达与癌症特征基因及通路（包括免疫逃逸、增殖和转移）之间的显著相关性。结论：这些发现表明微生物代谢物与MMRs的相互作用可能作为癌症诊断、预后评估和治疗的潜在生物标志物，凸显了其治疗潜力。本研究强调了微生物-癌症轴的重要意义，并为基于微生物组的癌症治疗策略提供了新的见解。
Pan-Cancer Insights: A Study of Microbial Metabolite Receptors in Malignancy Dynamics
肿瘤(癌症)患者之家