{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T04:54:43Z","timestamp":1774760083624,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oxford BioDynamics Plc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Colorectal cancer (CRC) arises from the epithelial lining of the colon or rectum, often following a progression from benign adenomatous polyps to malignant carcinoma. Screening modalities such as colonoscopy, faecal immunochemical tests (FIT), and FIT-DNA are critical for early detection and prevention, but non-invasive methods lack sensitivity to polyps and early CRC. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression. We have previously developed an epigenetic assay, EpiSwitch\u00ae\u00ae, that employs an algorithmic-based CCs analysis. Using EpiSwitch\u00ae\u00ae technology, we have shown the presence of cancer-specific CCs in peripheral blood mononuclear cells (PBMCs) and primary tumours of patients with melanoma and prostate cancer. EpiSwitch\u00ae\u00ae-based commercial tests are now available to diagnose prostate cancer with 94% accuracy (PSE test) and response to immune checkpoint inhibitors across 14 cancers with 85% accuracy (CiRT test). Methods\/Results\/Conclusions: Using blood samples collected from n = 171 patients with CRC, n = 44 patients with colorectal polyps and n = 110 patients with a \u2018clear\u2019 colonoscopy we performed whole Genome DNA screening for CCs correlating to CRC diagnosis. Our findings suggest the presence of two eight-marker CC signatures (EpiSwitch\u00ae\u00ae NST) in whole blood that allow diagnosis of CRC and precancerous polyps, respectively. Independent validation cohort testing demonstrated high accuracy in identifying colorectal polyps and early versus late stages of CRC with an exceptionally high sensitivity of 79\u201390% and a high positive prediction value of 60\u201384%. Linking the top diagnostic CCs to nearby genes, we have built pathways maps that likely underline processes contributing to the pathology of polyp and CRC progression, including TGF\u03b2, cMYC, Rho GTPase, ROS, TNFa\/NF\u03baB, and APC.<\/jats:p>","DOI":"10.3390\/cancers17030521","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T05:50:36Z","timestamp":1738734636000},"page":"521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A New Blood-Based Epigenetic Diagnostic Biomarker Test (EpiSwitch\u00ae\u00ae NST) with High Sensitivity and Positive Predictive Value for Colorectal Cancer and Precancerous Polyps"],"prefix":"10.3390","volume":"17","author":[{"given":"Ewan","family":"Hunter","sequence":"first","affiliation":[{"name":"Oxford BioDynamics Plc., Oxford OX4 2WB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba","family":"Alshaker","sequence":"additional","affiliation":[{"name":"Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cicely","family":"Weston","sequence":"additional","affiliation":[{"name":"Oxford BioDynamics Plc., Oxford OX4 2WB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutaz","family":"Issa","sequence":"additional","affiliation":[{"name":"Oxford BioDynamics Plc., Oxford OX4 2WB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shekinah","family":"Bautista","sequence":"additional","affiliation":[{"name":"Oxford BioDynamics Plc., Oxford OX4 2WB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel","family":"Gebregzabhar","sequence":"additional","affiliation":[{"name":"Oxford BioDynamics Plc., Oxford OX4 2WB, 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UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vamsi","family":"Velchuru","sequence":"additional","affiliation":[{"name":"James Paget University Hospitals NHS Trust, Great Yarmouth NR31 6LA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal","family":"Aryal","sequence":"additional","affiliation":[{"name":"James Paget University Hospitals NHS Trust, Great Yarmouth NR31 6LA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Radzi","family":"Bin Abu Hassan","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Hospital Sultanah Bahiyah, Jalan Langgar, Alor Setar 05460, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goh Tiong","family":"Meng","sequence":"additional","affiliation":[{"name":"Island Hospital Penang, Jalan Macalister, George Town 10450, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janisha Suriakant","family":"Patel","sequence":"additional","affiliation":[{"name":"Penang Reference Laboratory, Oxford BioDynamics Plc., Jalan Tanjung Tokong, George Town 10470, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shameera Pharveen","family":"Mohamed Gani","sequence":"additional","affiliation":[{"name":"Penang Reference Laboratory, Oxford BioDynamics Plc., Jalan Tanjung Tokong, George Town 10470, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun Ren","family":"Lim","sequence":"additional","affiliation":[{"name":"Penang Reference Laboratory, Oxford BioDynamics Plc., Jalan Tanjung Tokong, George Town 10470, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Guiel","sequence":"additional","affiliation":[{"name":"Oxford BioDynamics Inc., Frederick, MD 21703, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Akoulitchev","sequence":"additional","affiliation":[{"name":"Oxford BioDynamics Plc., Oxford OX4 2WB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-9261","authenticated-orcid":false,"given":"Dmitri","family":"Pchejetski","sequence":"additional","affiliation":[{"name":"Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","article-title":"Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from 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