Identification of microbial markers across populations in early detection of colorectal cancer

Yuanqi Wu, Na Jiao, Ruixin Zhu (), Yida Zhang, Dingfeng Wu, An-Jun Wang, Sa Fang, Liwen Tao, Yichen Li, Sijing Cheng, Xiaosheng He, Ping Lan, Chuan Tian (), Ning-Ning Liu () and Lixin Zhu ()
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Yuanqi Wu: Tongji University
Na Jiao: Sun Yat-sen University
Ruixin Zhu: Tongji University
Yida Zhang: Harvard Medical School
Dingfeng Wu: Tongji University
An-Jun Wang: Shanghai Jiao Tong University School of Medicine
Sa Fang: Tongji University
Liwen Tao: Tongji University
Yichen Li: Sun Yat-sen University
Sijing Cheng: Sun Yat-sen University
Xiaosheng He: Sun Yat-sen University
Ping Lan: Sun Yat-sen University
Chuan Tian: Tongji University
Ning-Ning Liu: Shanghai Jiao Tong University School of Medicine
Lixin Zhu: Sun Yat-sen University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23265-y

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