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Abstract
Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.
The gut microbiome plays an important role in colorectal carcinogenesis and predictive microbiome signatures have been proposed for colorectal cancer (CRC) diagnosis. Here the authors perform a meta-analysis of 16S rRNA-based profiles to identify microbial markers able to discriminate patients with adenoma from control and CRC, building a model that can be applied for the early detection of CRC.
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1 Tongji University, Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Shanghai, People’s Republic of China (GRID:grid.24516.34) (ISNI:0000000123704535)
2 Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Guangzhou, People’s Republic of China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
3 Harvard Medical School, Department of Biomedical Informatics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
4 Shanghai Jiao Tong University School of Medicine, State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai, People’s Republic of China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
5 Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Guangzhou, People’s Republic of China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); School of Medicine, Sun Yat-sen University, Shenzhen, People’s Republic of China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
6 Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Guangzhou, People’s Republic of China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); The State University of New York at Buffalo, Genome, Environment and Microbiome Community of Excellence, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887)