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

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 (c...

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Autores principales: Cao, Feng, Wei, Ailin, Hu, Xinlei, He, Yijing, Zhang, Jun, Xia, Lin, Tu, Kailing, Yuan, Jue, Guo, Ziheng, Liu, Hongying, Xie, Dan, Li, Ang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376965/
https://www.ncbi.nlm.nih.gov/pubmed/32703318
http://dx.doi.org/10.1186/s13148-020-00898-2
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author Cao, Feng
Wei, Ailin
Hu, Xinlei
He, Yijing
Zhang, Jun
Xia, Lin
Tu, Kailing
Yuan, Jue
Guo, Ziheng
Liu, Hongying
Xie, Dan
Li, Ang
author_facet Cao, Feng
Wei, Ailin
Hu, Xinlei
He, Yijing
Zhang, Jun
Xia, Lin
Tu, Kailing
Yuan, Jue
Guo, Ziheng
Liu, Hongying
Xie, Dan
Li, Ang
author_sort Cao, Feng
collection PubMed
description 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: [Image: see text]
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spelling pubmed-73769652020-08-04 Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer Cao, Feng Wei, Ailin Hu, Xinlei He, Yijing Zhang, Jun Xia, Lin Tu, Kailing Yuan, Jue Guo, Ziheng Liu, Hongying Xie, Dan Li, Ang Clin Epigenetics Research 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: [Image: see text] BioMed Central 2020-07-23 /pmc/articles/PMC7376965/ /pubmed/32703318 http://dx.doi.org/10.1186/s13148-020-00898-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cao, Feng
Wei, Ailin
Hu, Xinlei
He, Yijing
Zhang, Jun
Xia, Lin
Tu, Kailing
Yuan, Jue
Guo, Ziheng
Liu, Hongying
Xie, Dan
Li, Ang
Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
title Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
title_full Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
title_fullStr Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
title_full_unstemmed Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
title_short Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer
title_sort integrated epigenetic biomarkers in circulating cell-free dna as a robust classifier for pancreatic cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376965/
https://www.ncbi.nlm.nih.gov/pubmed/32703318
http://dx.doi.org/10.1186/s13148-020-00898-2
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