| Title: |
5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer. |
| Authors: |
Puddu, Fabio; Johansson, Annelie; Modat, Aurélie; Scotcher, Jamie; Sethi, Riccha; Yu, Shirong; Harding, Nick; Hill, Mark; Lleshi, Ermira; Lumby, Casper; Teyssandier, Jean; Wilson, Michael; Crawford, Robert; Charlesworth, Tom; Creed, Páidí; Balasubramanian, Shankar; Osborne, Robert J |
| Publisher Information: |
Springer Nature; //doi.org/10.1038/s43856-025-01278-8 |
| Publication Year: |
2026 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
32 Biomedical and Clinical Sciences; 3211 Oncology and Carcinogenesis; Genetic Testing; Human Genome; Colo-Rectal Cancer; Prevention; Women's Health; Digestive Diseases; Cancer Genomics; Genetics; Cancer; 4.1 Discovery and preclinical testing of markers and technologies; 4.2 Evaluation of markers and technologies |
| Description: |
BACKGROUND: Early cancer detection has the potential to significantly improve treatment outcomes and survival rates. This study investigates the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). METHODS: We analyzed cfDNA from 37 treatment-naive CRC patients and 32 healthy controls using duet evoC 6-base whole genome sequencing (A, C, T, G, 5mC, 5hmC). We then built CRC classifiers using differentially methylated regions identified in stage IV CRC tissue samples. We compared the performance of models using 5mC-only, 5hmC-only, modified cytosine, or 5mC and 5hmC features. RESULTS: Here we show that models combining measurements of 5mC and 5hmC significantly enhance diagnostic accuracy (AUC = 0.95) compared to traditional approaches that conflate these markers (modified C, AUC = 0.66). Notably, of all the DMRs considered, almost half show an increase in 5hmC at stage I and a corresponding decrease in 5mC at stage IV, suggesting that 5hmC can effectively track regions undergoing demethylation during tumor development. CONCLUSIONS: These results support the hypothesis that distinguishing between 5mC and 5hmC improves the sensitivity of liquid biopsy tests for early-stage cancer detection. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/zip; application/pdf; text/xml |
| Language: |
English |
| Relation: |
1278; https://www.repository.cam.ac.uk/handle/1810/395717 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/395717 |
| Accession Number: |
edsbas.63C7994D |
| Database: |
BASE |