Taxonomic and functional profiling of fecal metagenomes for the early detection of colorectal cancer

Xudong Wu; Zhimin Tang; Rongsong Zhao; Yusi Wang; Xianshu Wang; Side Liu; Hongzhi Zou

doi:10.3389/fonc.2023.1218056

Taxonomic and functional profiling of fecal metagenomes for the early detection of colorectal cancer

Front Oncol. 2023 Aug 3:13:1218056. doi: 10.3389/fonc.2023.1218056. eCollection 2023.

Authors

Xudong Wu¹, Zhimin Tang¹, Rongsong Zhao¹, Yusi Wang², Xianshu Wang¹, Side Liu², Hongzhi Zou^{1

3}

Affiliations

¹ Creative Biosciences (Guangzhou) CO., Ltd, Guangzhou, Guangdong, China.
² Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
³ Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Abstract

Objectives: This 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.

Methods: We 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.

Results: A diverse spectrum of bacterial and fungi species were found to be either enriched (368) or reduced (113) in CRC patients (q<0.05). Similarly, metabolic functions associated with biosynthesis and metabolism of amino acids and fatty acids were significantly altered (q<0.05). The LASSO regression analysis of significant changes in the abundance of microbial species in CRC achieved areas under the receiver operating characteristic curve (AUROCs) of 0.94 and 0.91 in the ZhongShanMed and SouthernMed cohorts, respectively. A further analysis of Fudan, GloriousMed, and HK cohorts using the same classification model also demonstrated AUROC of 0.80, 0.78, and 0.91, respectively. Moreover, major CRC-associated bacterial biomarkers identified in this study were found to be coherently enriched or depleted across 10 metagenomic sequencing studies of gut microbiota.

Conclusion: A coherent signature of CRC-associated bacterial biomarkers modeled on LASSO binomial classifier maybe used accurately for early detection of CRC.

Keywords: bacterial biomarker; fecal microbiota; functional pathways; metagenomic sequencing; microbial taxonomy.

Grants and funding

The work was supported by National Key Research and Development Program of China (2017YFC1308800 to PL and HZ), Leadership Program of Guangzhou Talent Project to HZ (Grant No. 2016018 to HZ), Leadership Program of Talent Project of Guangdong Province to HZ (Grant No. 2016LJ06S544 to HZ), and Talent Project of Innovation and Entrepreneurship in Developmental Zone of Guangzhou (Grant No. 2017-L1772022-L025 to HZ).