Application of fecal DNA multi-gene methylation testing in colorectal cancer screening in Haikou City

doi:10.4251/wjgo.123758

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Oct 15, 2026; 18(10): 123758
Published online Oct 15, 2026. doi: 10.4251/wjgo.123758

Application of fecal DNA multi-gene methylation testing in colorectal cancer screening in Haikou City

Run-Yu Chen, Da-Ya Zhang, Yu-Liang Huang, Jun-Min Yao, Xiao Zhong, Ping-Ping Li, Fei-Hu Bai

Run-Yu Chen, Da-Ya Zhang, Yu-Liang Huang, Jun-Min Yao, Xiao Zhong, Ping-Ping Li, Fei-Hu Bai, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, Hainan Province, China

Co-first authors: Run-Yu Chen and Da-Ya Zhang.

Author contributions: Chen RY, Zhang DY and Bai FH drafted the manuscript; Chen RY and Bai FH designed the study and performed statistical analysis; Yao JM and Huang YL recruited participants; Chen RY, Zhang DY, Huang YL, Yao JM, Zhong X, Li PP, and Bai FH collected data; Chen RY and Zhang DY contributed equally to this manuscript and are co-first authors. All authors read and approved the final manuscript.

AI contribution statement: Not applicable, as no AI tools were used in the research or manuscript preparation.

Supported by Flexible Talent Introduction Collaborative Innovation Center, Hainan Medical University Academic Enhancement Support Program, No. XSTS2025001 and No. XSTS2026051; Joint Project on Health Science and Technology Innovation in Hainan Province, No. WSJK2024MS150; Hainan Medical University Undergraduate Research Innovation Program, No. RZ2600001129; Hainan Province Education Reform Project, No. hnjg2024-67; and National Clinical Key Specialty Capacity Building Project, No. 202330.

Institutional review board statement: This study was approved by the Ethics Committees of the Second Affiliated Hospital of Hainan Medical University (Approval No. 2026-K49-01). All procedures involving human participants were conducted in accordance with the Declaration of Helsinki, and all methods were performed following relevant guidelines and regulations.

Informed consent statement: Informed consent was obtained from all subjects involved in the study.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The datasets used and/or analyzed in this study can be reasonably obtained from the corresponding author.

Corresponding author: Fei-Hu Bai, Chief Physician, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, No. 368 Yehai Avenue, Longhua District, Haikou 570216, Hainan Province, China. hy214654@muhn.edu.cn

Received: May 28, 2026
Revised: June 22, 2026
Accepted: July 6, 2026
Published online: October 15, 2026
Processing time: 114 Days and 17.9 Hours

Abstract

BACKGROUND

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with incidence and mortality rates continuing to rise. Early diagnosis and prevention are essential for reducing the disease burden. Fecal DNA methylation testing is a non-invasive method for CRC screening.

AIM

To evaluate the clinical utility of a fecal multi-gene methylation assay targeting three genes, syndecan 2 (SDC2), alcohol dehydrogenase, iron containing 1 (ADHFE1), and protein phosphatase 2 regulatory subunit B’ gamma (PPP2R5C), for early CRC screening in Haikou City and to identify risk factors associated with positive screening results.

METHODS

This study was conducted across five administrative districts of Haikou City, Hainan Province, from July 1, 2025 to May 1, 2026. Enrolled participants completed a questionnaire on CRC-related risk factors and provided fecal samples. The promoter methylation status of SDC2, ADHFE1, and PPP2R5C in exfoliated cells from stool samples was assessed using quantitative real-time polymerase chain reaction. With colonoscopy and histopathology as the gold standard, the positive predictive value (PPV) of the multi-gene methylation test was calculated for CRC, advanced adenoma, non-advanced adenoma, and polyps. Univariate χ² tests and binary logistic regression models were used to identify factors associated with positive screening results and independent risk factors.

RESULTS

A total of 4050 participants were included, with an initial screening positivity rate of 5.16% (209/4050). Among those with positive results, 128 (61.2%) underwent colonoscopy, which identified 4 cases of CRC (3.1%), 19 cases of advanced adenoma (14.8%), 86 cases of non-advanced adenoma or polyps (67.2%), and 19 cases with normal colonoscopy findings (14.8%). The PPV of the test for any colorectal lesion was 85.2% (109/128). Univariate and multivariate logistic regression analyses identified increasing age [odds ratio (OR) = 1.672, 95% confidence interval (CI): 1.245-2.245], Helicobacter pylori infection (OR = 1.777, 95%CI: 1.329-2.376), a long-term high-salt diet (OR = 2.596, 95%CI: 1.829–3.685), and consumption of pickled foods (OR = 1.827, 95%CI: 1.299-2.570) as independent risk factors for positive screening results (all P < 0.05).

CONCLUSION

The fecal multi-gene methylation test based on SDC2, ADHFE1, and PPP2R5C showed a high PPV (85.2%) for CRC screening in Hainan Province and effectively enriched for colorectal lesions. This non-invasive and convenient testing method may be a feasible strategy for large-scale CRC screening in Hainan Province. Future efforts should focus on improving compliance with follow-up colonoscopy.

Keywords: Colorectal cancer; Fecal DNA methylation; Syndecan 2; Alcohol dehydrogenase, iron containing 1; Protein phosphatase 2 regulatory subunit B’ gamma; Positive predictive value; Early screening

Core Tip: This cross-sectional study evaluated fecal DNA multi-gene methylation testing (syndecan 2/alcohol dehydrogenase, iron containing 1/protein phosphatase 2 regulatory subunit B’ gamma) in 4050 participants in Haikou City, Hainan Province, China. The test demonstrated a high positive predictive value (85.2%) for detecting colorectal lesions and identified independent risk factors associated with positive screening results, such as older age, Helicobacter pylori infection, high-salt diet, and pickled food consumption. These findings support its potential as a non-invasive colorectal cancer screening tool in Hainan Province.