越来越多的证据支持人类微生物组在肿瘤的发展和治疗反应中的重要作用。循环微生物 DNA 是非侵入性的，可以显示宿主微生物组的总体情况，使其成为有前途的癌症生物标志物。然而，循环微生物组是否与非小细胞肺癌（NSCLC）预后相关及其对肿瘤免疫微环境的潜在机制仍不清楚。TCGA NSCLC患者的血液微生物组数据和匹配的肿瘤RNA-seq数据来自Poore's研究和UCSC Xena。使用单变量和多变量 Cox 回归分析来识别与总生存 (OS) 相关的循环微生物组特征，并构建循环微生物丰度预后评分 (MAPS) 模型。建立整合临床特征和循环 MAPS 评分的列线图来预测 NSCLC 患者的 OS 率。使用血液微生物组数据和匹配的肿瘤 RNA-seq 数据的联合分析来解读循环 MAPS 高和 MAPS 低组患者的肿瘤微环境景观。最后评估循环MAPS对免疫治疗和化疗疗效的预测价值。构建了由14种循环微生物组成的循环MAPS预测模型，对NSCLC具有独立的预后价值。将循环 MAPS 整合到列线图中可以提高预后预测能力。联合分析揭示了预后循环微生物组与肿瘤免疫微环境之间的潜在相互作用。特别是，循环MAPS低组中肿瘤内浆细胞和体液免疫反应丰富，而MAPS高组中肿瘤内CD4  Th2细胞和增殖相关途径丰富。最后，药物敏感性分析表明循环MAPS作为化疗疗效预测因子的潜力。成功构建了循环MAPS预测模型，该模型对NSCLC具有重要的预后价值。我们的研究提供了关于微生物、肿瘤和免疫之间相互作用的新见解，并可能进一步为 NSCLC 的精准医疗做出贡献。© 2023。作者。

Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown.The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore's study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed.A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4 + Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy.A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC.© 2023. The Author(s).