Integrated multi-omics profiling reveals phenotype- and tissue-specific host-microbiota interactions in paired tumor and peritumoral tissues of advanced gastric cancer patients from Northwest China

Background: Advanced gastric cancer (AGC) exhibits a high incidence in Northwest China, largely attributed to region-specific dietary patterns and environmental exposures. Its pathogenesis involves complex host-microbiota crosstalk, which has not yet been comprehensively elucidated through integrated multi-omics approaches. Herein, we employed trasncriptomic and shotgun metagenomic sequencing on paired tumoral and peritumoal mucosal tissues from 88 AGC patients in Northwest China. Our aim was to systematically characterize host gene expression profiles, the composition and functional potential of the gastric mucosal microbiota, and their intricate interrelationships. Results: exhibited the strongest connectivity with host genes. Functionally, the correlated DEGs were involved in ECM structure, cell cycle progression, immune and inflammatory responses, cellular proliferation and differentiation, and metabolic processes. Conclusions: Our findings demonstrated phenotype- and tissue-specific regulation of host gene expression in AGC and revealed extensive host-microbe interactions. This work fills a critical gap in multi-omics research on AGC in the Northwest Chinese population and suggests potential diagnostic and therapeutic targets for AGC.