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Stool- and Blood-Associated Colorectal Cancer Biomarkers: A Systematic Review
by
,
Pumelela Hallom
1,2,*, 
Pragalathan Naidoo
1,2,
Sibusiso Senzani
1,
Sayed S. Kader
3 and
Zilungile L. Mkhize-Kwitshana
1,2,4,* 1
Department of Medical Microbiology, School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Nelson R. Mandela Medical School Campus, Durban 4001, South Africa
2
Division of Research Capacity Development (RCD), South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa
3
Department of Surgery, University of KwaZulu Natal, Congella, Durban 4013, South Africa
4
Biomedical Sciences Department, School of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida Campus, Johannesburg 1710, South Africa
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(1), 96; https://doi.org/10.3390/cancers18010096 (registering DOI)
Submission received: 18 November 2025
/
Revised: 12 December 2025
/
Accepted: 21 December 2025
/
Published: 27 December 2025
(This article belongs to the Section Cancer Biomarkers)
Simple Summary
Colorectal cancer is one of the most common and deadly cancers worldwide, but many people are diagnosed too late because current screening tests are expensive, invasive, or not easily available. Early detection greatly increases the chances of successful treatment. This research aims to find simple, accurate, and non-invasive ways to detect colorectal cancer using biological markers found in blood and stool. These markers can reveal early changes in the body that happen before cancer develops. By reviewing the most promising blood and stool markers, this study highlights potential tools that could make screening easier and more accessible for everyone. The findings may guide future research toward developing affordable tests that can detect colorectal cancer earlier, reduce deaths, and improve global health outcomes.
Abstract
Background/Objectives: Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide. While existing screening tools are effective, their high cost and limited availability restrict widespread adoption, particularly in low- and middle-income settings. The identification of affordable, non-invasive biomarkers is therefore critical to improve early CRC detection and survival outcomes. Methods: A systematic literature search was performed through PubMed, ScienceDirect, Medline, ISI Web of Knowledge, and Google Scholar to identify studies reporting stool- and blood-based biomarkers for CRC detection. Data were extracted using a standardized template, including study details, specimen type, detection method, and diagnostic performance parameters such as sensitivity and specificity. Results: DNA methylation biomarkers demonstrated high diagnostic potential. Syndecan 2 (SDC2) and Short Stature Homeobox 2 (SHOX2) achieved a combined stool sensitivity of 91.35%. Other methylation markers, including NDRG4, SEPT9, and BCAT1, showed a composite sensitivity of 82.7%. Plasma-based methylation markers such as GATA5, FOXE1, and SYNE1 reported sensitivities ranging from 18–47% and specificities of 93–99%. Hypermethylation of SFRP2 and WIF-1 achieved 81.3% sensitivity in CRC and precursor lesions. Matrix metalloproteinases (MMP-2 and MMP-9) were elevated in CRC patients, with stool MMP-9 yielding 72.2% sensitivity and 95% specificity. A stool gene panel (UBE2N, IMPDH1, DYNC1LI1, HRASLS2) reached 96.6% sensitivity and 89.7% specificity, while a methylation-based panel (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM) achieved 90.7% sensitivity. MicroRNAs (miR-21, miR-92a, miR-223, miR-182) showed excellent diagnostic performance, with sensitivities exceeding 96% and specificities above 75%. Conclusions: DNA methylation and microRNA biomarkers hold strong promises for non-invasive CRC screening. Multi-marker panels demonstrate superior diagnostic accuracy and may provide a cost-effective, scalable approach for early CRC detection in resource-limited settings.
Keywords:
blood; stool; biomarkers; colorectal cancer; non-invasive screening methods
