{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:02:41Z","timestamp":1792598561315,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u201347% and specificities of 93\u201399%. 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.<\/jats:p>","DOI":"10.3390\/cancers18010096","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:47:27Z","timestamp":1766998047000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stool- and Blood-Associated Colorectal Cancer Biomarkers: A Systematic Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Pumelela","family":"Hallom","sequence":"first","affiliation":[{"name":"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"},{"name":"Division of Research Capacity Development (RCD), South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-5926","authenticated-orcid":false,"given":"Pragalathan","family":"Naidoo","sequence":"additional","affiliation":[{"name":"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"},{"name":"Division of Research Capacity Development (RCD), South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibusiso","family":"Senzani","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed S.","family":"Kader","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of KwaZulu Natal, Congella, Durban 4013, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilungile L.","family":"Mkhize-Kwitshana","sequence":"additional","affiliation":[{"name":"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"},{"name":"Division of Research Capacity Development (RCD), South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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