Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer

• Published in: Clinical epigenetics 2020-07, Vol.12 (1), p.112-112, Article 112
• Main Authors: Cao, Feng, Wei, Ailin, Hu, Xinlei, He, Yijing, Zhang, Jun, Xia, Lin, Tu, Kailing, Yuan, Jue, Guo, Ziheng, Liu, Hongying, Xie, Dan, Li, Ang
• Format: Article
• Language: English
• Subjects: 5-Methylcytosine - analogs & derivatives; 5-Methylcytosine - blood; Adenocarcinoma; Adenocarcinoma - blood; Analysis; Biological markers; Biomarkers; Biomarkers, Tumor - blood; Cancer genetics; Carcinoma, Pancreatic Ductal - blood; Cell-Free Nucleic Acids - blood; Deoxyribonucleic acid; Diagnosis; DNA; DNA methylation; Epigenesis, Genetic - physiology; Epigenetic inheritance; Epigenetics; Female; Gene expression; Genomes; Genomics; Humans; Male; Methods; Middle Aged; Mutation; Pancreatic cancer; Pancreatic Neoplasms - blood; Prediction models; Reproducibility of Results; Sensitivity and Specificity
• ISSN: 1868-7075; 1868-7083; 1868-7083; 1868-7075
• DOI: 10.1186/s13148-020-00898-2

The high lethal rate of pancreatic cancer is partly due to a lack of efficient biomarkers for screening and early diagnosis. We attempted to develop effective and noninvasive methods using 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) markers from circulating cell-free DNA (cfDNA) for the detection of pancreatic ductal adenocarcinoma (PDAC). A 24-feature 5mC model that can accurately discriminate PDAC from healthy controls (area under the curve (AUC) = 0.977, sensitivity = 0.824, specificity = 1) and a 5hmC prediction model with 27 features demonstrated excellent detection power in two distinct validation sets (AUC = 0.992 and 0.960, sensitivity = 0.786 and 0.857, specificity = 1 and 0.993). The 51-feature model combining 5mC and 5hmC markers outperformed both of the individual models, with an AUC of 0.997 (sensitivity = 0.938, specificity = 0.955) and particularly an improvement in the prediction sensitivity of PDAC. In addition, the weighted diagnosis score (wd-score) calculated with the 5hmC model can distinguish stage I patients from stage II-IV patients. Both 5mC and 5hmC biomarkers in cfDNA are effective in PDAC detection, and the 5mC-5hmC integrated model significantly improve the detection sensitivity.