Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2023; 15(8): 1424-1435
Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1424
Fecal microbial biomarkers combined with multi-target stool DNA test improve diagnostic accuracy for colorectal cancer
Jin-Qing Fan, Wang-Fang Zhao, Qi-Wen Lu, Fu-Rong Zha, Le-Bin Lv, Guo-Liang Ye, Han-Lu Gao
Jin-Qing Fan, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
Wang-Fang Zhao, Qi-Wen Lu, Guo-Liang Ye, Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
Fu-Rong Zha, Department of Bioinformation Analysis, Shanghai BIOZERON Biotechnology Co., Shanghai 201800, China
Le-Bin Lv, Han-Lu Gao, Department of Preventive Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
Author contributions: Fan JQ collected the clinical data and wrote the original manuscript; Zhao WF, Lu QW, and Ye GL participated in the collection of human material; Lv LB performed data collection and collation; Zha FR performed bioinformatics analysis; Gao HL conceived the research and edited the manuscript.
Supported by the Medical and Health Research Project of Zhejiang Province, No. 2021KY1048 and 2022KY1142; Ningbo Health Young Technical Backbone Talents Training Program, No. 2020SWSQNGG-02; and the Key Science and Technology Project of Ningbo City, No. 2021Z133.
Institutional review board statement: The study was approved by the Human Research and Ethics Committee of the Affiliated Hospital of Medical School of Ningbo University (approval number: KY20211104).
Informed consent statement: All the participants provided written informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE statement, and the manuscript was prepared and revised according to the STROBE statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Han-Lu Gao, PhD, Doctor, Department of Preventive Medicine, The First Affiliated Hospital of Ningbo University, No. 247 Renmin Road, Ningbo 315000, Zhejiang Province, China. 306646058@qq.com
Received: March 24, 2023
Peer-review started: March 24, 2023
First decision: May 19, 2023
Revised: May 20, 2023
Accepted: June 19, 2023
Article in press: June 19, 2023
Published online: August 15, 2023
Processing time: 139 Days and 5 Hours
Abstract
BACKGROUND

Colorectal cancer (CRC) is a major global health burden. The current diagnostic tests have shortcomings of being invasive and low accuracy.

AIM

To explore the combination of intestinal microbiome composition and multi-target stool DNA (MT-sDNA) test in the diagnosis of CRC.

METHODS

We assessed the performance of the MT-sDNA test based on a hospital clinical trial. The intestinal microbiota was tested using 16S rRNA gene sequencing. This case-control study enrolled 54 CRC patients and 51 healthy controls. We identified biomarkers of bacterial structure, analyzed the relationship between different tumor markers and the relative abundance of related flora components, and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size, redundancy analysis, and random forest analysis.

RESULTS

MT-sDNA was associated with Bacteroides. MT-sDNA and carcinoembryonic antigen (CEA) were positively correlated with the existence of Parabacteroides, and alpha-fetoprotein (AFP) was positively associated with Faecalibacterium and Megamonas. In the random forest model, the existence of Streptococcus, Escherichia, Chitinophaga, Parasutterella, Lachnospira, and Romboutsia can distinguish CRC from health controls. The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%, with a sensitivity and specificity of 98.1% and 92.3%, respectively.

CONCLUSION

There is a positive correlation of MT-sDNA, CEA, and AFP with intestinal microbiome. Eight biomarkers including six genera of gut microbiota, MT-sDNA, and CEA showed a prominent sensitivity and specificity for CRC prediction, which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.

Keywords: Gut microbiome; Colorectal cancer; Diagnostic model; Multi-target stool DNA test; Tumor biomarker

Core Tip: There is a positive correlation of multi-target stool DNA (MT-sDNA), carcinoembryonic antigen (CEA), and alpha-fetoprotein with intestinal microbiome. Eight biomarkers including six genera of gut microbiota, MT-sDNA, and CEA showed a prominent sensitivity (98.1%) and specificity (92.3%) for colorectal cancer prediction, which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.