Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
Posted on 2020-07-24 - 03:58
Abstract Background 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). Results 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. Conclusions Both 5mC and 5hmC biomarkers in cfDNA are effective in PDAC detection, and the 5mC-5hmC integrated model significantly improve the detection sensitivity. Graphical abstract
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Cao, Feng; Wei, Ailin; Hu, Xinlei; He, Yijing; Zhang, Jun; Xia, Lin; et al. (2020). Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5072006.v1