Leveraging circulating microbiome signatures to predict tumor immune microenvironment and prognosis of patients with non-small cell lung cancer.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.