metagenomic sequencing, fecal microbiota, bacterial biomarker, microbial taxonomy, functional pathways, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

ObjectivesThis study aimed to identify colorectal cancer (CRC)-associated phylogenetic and functional bacterial features by a large-scale metagenomic sequencing and develop a binomial classifier to accurately distinguish between CRC patients and healthy individuals.MethodsWe conducted shotgun metagenomic analyses of fecal samples from a ZhongShanMed discovery cohort of 121 CRC and 52 controls and SouthernMed validation cohort of 67 CRC and 44 controls. Taxonomic profiling and quantification were performed by direct sequence alignment against genome taxonomy database (GTDB). High-quality reads were also aligned to IGC datasets to obtain functional profiles defined by Kyoto Encyclopedia of Genes and Genomes (KEGG). A least absolute shrinkage and selection operator (LASSO) classifier was constructed to quantify risk scores of probability of disease and to discriminate CRC from normal for discovery, validation, Fudan, GloriousMed, and HongKong cohorts.ResultsA diverse spectrum of bacterial and fungi species were found to be either enriched (368) or reduced (113) in CRC patients (q