Methods: A retrospective analysis using bisulphite pyrosequencing of an 11 marker panel (SFRP1, SFRP2, SRP4, SRP5, WIF1, TUBB6, SOX7, APC1A, APC2, MINT1, RUNX3) in samples from35 patients with cancer, 78with dysplasia and 343 without neoplasia undergoing surveillance for UC associated neoplasia across 6 medical centres. Predictive models for UC associated cancer/dysplasia were created in the setting of neoplastic and non-neoplastic mucosa.
Findings: For neoplasticmucosa a five marker panel (SFRP2, SFRP4, WIF1, APC1A, APC2) was accurate in detecting pre-cancerous and invasive neoplasia (AUC=0.83; 95% CI: 0.79, 0.88), and dysplasia (AUC=0.88; (0.84, 0.91).
For non-neoplastic mucosa a four marker panel (APC1A, SFRP4, SFRP5, SOX7) had modest accuracy (AUC=0.68; 95% CI: 0.62,0.73) in predicting associated bowel neoplasia through the methylation signature of distant nonneoplastic colonic mucosa.
Interpretation: This multiplex methylation marker panel is accurate in the detection of ulcerative colitis associated dysplasia and neoplasia and is currently being validated in a prospective clinical trial.
Funding: The ENDCAP-C study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) Programme (11/100/29).
- Biomarkers, Tumor/genetics
- Colitis, Ulcerative/complications
- Colonic Neoplasms/diagnosis
- DNA Methylation
- Epigenesis, Genetic
- Prospective Studies
- Retrospective Studies
- Sequence Analysis, DNA/methods