Identifying potential DNA methylation markers in early-stage colorectal Cancer.

Abstract Colorectal cancer (CRC) is the second leading malignancy worldwide. Accurate screening is pivotal to early CRC detection, yet current screening modality involves invasive colonoscopy while non-invasive FIT tests have limited sensitivity. We applied a DNA methylation assay to identify biomarkers for early-stage CRC detection, risk stratification and precancerous lesion screening at tissue level. A model of biomarkers SFMBT2, ITGA4, THBD and ZNF304 showed 96.1% sensitivity and 87% specificity in CRC detection, with 100% sensitivity for advanced precancerous lesion and stage I CRC. Performances were further validated with TCGA data set, which showed a consistent AUC of 0.99 and exhibited specificity against other cancer types. KCNJ12, VAV3-AS1 and EVC were further identified for stage stratification (stage 0-I versus stage II-IV), with AUC of 0.87, 83.0% sensitivity and 71.2% specificity. Additionally, dual markers of NEUROD1 and FAM72C showed 83.2% sensitivity and 77.4% specificity in differing non-advanced precancerous lesions from inflammatory bowel diseases.