1. Identifying potential DNA methylation markers in early-stage colorectal Cancer.
- Author
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Zhang, Xiaoyu, Wan, Shenmei, Yu, Yanqi, Ruan, Weimei, Wang, Hong, Xu, Linhao, Wang, Chanjuan, Chen, Shang, Cao, Tianfeng, Peng, Quanzhou, Li, Sihui, Hu, Tianliang, Jiang, Zeyu, Chen, Zhiwei, and Fan, Jian-Bing
- Subjects
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GENETIC markers , *COLORECTAL cancer , *INFLAMMATORY bowel diseases , *HISTONE methylation , *PRECANCEROUS conditions , *DNA methylation , *METHYLATION - 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 87.0% specificity in CRC detection, with 100.0% 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. • Three sets of methylation markers for CRC management were identified at tissue level. • SFMBT2, ITGA4, THBD and ZNF304 were markers for early-stage CRC detection. • Methylation of KCNJ12, VAV3-AS1 and EVC were identified for CRC stage stratification. • NEUROD1 and FAM72C differentiated non-advanced precancerous lesions from IBD. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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