A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers

Background: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compl...

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Main Authors: Yanmiao Dai, Hui Li, Qianqian Wu, Jie Wang, Kai Wang, Sujuan Fei, Bing Pei, Lishuang Song, Guangxia Chen, Yong Ma, Chenjing Xia, Shangmin Xiong, Minxue Zheng, Ying Xue, Guodong Zhao, Hongwei Xu
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Neoplasia: An International Journal for Oncology Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558623000659
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author Yanmiao Dai
Hui Li
Qianqian Wu
Jie Wang
Kai Wang
Sujuan Fei
Bing Pei
Lishuang Song
Guangxia Chen
Yong Ma
Chenjing Xia
Shangmin Xiong
Minxue Zheng
Ying Xue
Guodong Zhao
Hongwei Xu
author_facet Yanmiao Dai
Hui Li
Qianqian Wu
Jie Wang
Kai Wang
Sujuan Fei
Bing Pei
Lishuang Song
Guangxia Chen
Yong Ma
Chenjing Xia
Shangmin Xiong
Minxue Zheng
Ying Xue
Guodong Zhao
Hongwei Xu
author_sort Yanmiao Dai
collection DOAJ
description Background: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. Methods: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. Results: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). Conclusion: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.
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spelling doaj.art-2b0f6fdb80f04d0c93c221a80659634b2023-11-30T05:06:15ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862023-12-0146100941A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancersYanmiao Dai0Hui Li1Qianqian Wu2Jie Wang3Kai Wang4Sujuan Fei5Bing Pei6Lishuang Song7Guangxia Chen8Yong Ma9Chenjing Xia10Shangmin Xiong11Minxue Zheng12Ying Xue13Guodong Zhao14Hongwei Xu15Department of Spleen and Stomach Diseases, Kunshan Hospital of traditional Chinese Medicine, Kunshan Jiangsu 215300, ChinaDepartment of Gastroenterology, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou Jiangsu 221002, China; Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Jiangsu 221002, ChinaDepartment of Gastroenterology, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou Jiangsu 221002, ChinaDepartment of Spleen and Stomach Diseases, Kunshan Hospital of traditional Chinese Medicine, Kunshan Jiangsu 215300, ChinaSuzhou VersaBio Technologies Co. Ltd., Kunshan Jiangsu 215300, ChinaDepartment of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Jiangsu 221002, ChinaDepartment of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu, 223800, ChinaSuzhou VersaBio Technologies Co. Ltd., Kunshan Jiangsu 215300, ChinaDepartment of Gastroenterology, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou Jiangsu 221002, ChinaZhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan Jiangsu 215300, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou Jiangsu 215163, ChinaDepartment of Spleen and Stomach Diseases, Kunshan Hospital of traditional Chinese Medicine, Kunshan Jiangsu 215300, ChinaZhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan Jiangsu 215300, China; Suzhou VersaBio Technologies Co. Ltd., Kunshan Jiangsu 215300, ChinaZhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan Jiangsu 215300, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou Jiangsu 215163, ChinaThe Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou Jiangsu 215000, China; Corresponding authors.Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan Jiangsu 215300, China; Suzhou VersaBio Technologies Co. Ltd., Kunshan Jiangsu 215300, China; Corresponding authors.Department of Spleen and Stomach Diseases, Kunshan Hospital of traditional Chinese Medicine, Kunshan Jiangsu 215300, China; Corresponding author at: Department of Spleen and Stomach Diseases, Kunshan Hospital of traditional Chinese Medicine, Kunshan Jiangsu 215300, China.Background: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. Methods: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. Results: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). Conclusion: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.http://www.sciencedirect.com/science/article/pii/S1476558623000659Gastrointestinal cancersDNA methylationPlasmaCost-effectiveNon-invasive
spellingShingle Yanmiao Dai
Hui Li
Qianqian Wu
Jie Wang
Kai Wang
Sujuan Fei
Bing Pei
Lishuang Song
Guangxia Chen
Yong Ma
Chenjing Xia
Shangmin Xiong
Minxue Zheng
Ying Xue
Guodong Zhao
Hongwei Xu
A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
Neoplasia: An International Journal for Oncology Research
Gastrointestinal cancers
DNA methylation
Plasma
Cost-effective
Non-invasive
title A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
title_full A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
title_fullStr A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
title_full_unstemmed A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
title_short A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers
title_sort sensitive and robust plasma based dna methylation panel for early detection of target gastrointestinal cancers
topic Gastrointestinal cancers
DNA methylation
Plasma
Cost-effective
Non-invasive
url http://www.sciencedirect.com/science/article/pii/S1476558623000659
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