A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection

Background: Upper gastrointestinal cancer (UGC) is an important cause of cancer death in China, with low five-year survival rates due to the majority of UGC patients being diagnosed at an advanced stage. Therefore, there is an urgent need to develop cost-effective, reliable and non-invasive methods...

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Main Authors: Cheng Peng, Guodong Zhao, Bing Pei, Kai Wang, Hui Li, Sujuan Fei, Lishuang Song, Chunkai Wang, Shangmin Xiong, Ying Xue, Qibin He, Minxue Zheng
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/21/5282
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author Cheng Peng
Guodong Zhao
Bing Pei
Kai Wang
Hui Li
Sujuan Fei
Lishuang Song
Chunkai Wang
Shangmin Xiong
Ying Xue
Qibin He
Minxue Zheng
author_facet Cheng Peng
Guodong Zhao
Bing Pei
Kai Wang
Hui Li
Sujuan Fei
Lishuang Song
Chunkai Wang
Shangmin Xiong
Ying Xue
Qibin He
Minxue Zheng
author_sort Cheng Peng
collection DOAJ
description Background: Upper gastrointestinal cancer (UGC) is an important cause of cancer death in China, with low five-year survival rates due to the majority of UGC patients being diagnosed at an advanced stage. Therefore, there is an urgent need to develop cost-effective, reliable and non-invasive methods for the early detection of UGC. Methods: A novel plasma-based methylation panel combining simultaneous detection of three methylated biomarkers (<i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i>) and an internal control gene were developed and used to examine plasma samples from 186 UGC patients and 190 control subjects. Results: The results indicated excellent PCR amplification efficiency and reproducibility of <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> in the range of 10–100,000 copies per PCR reaction of fully methylated genomic DNA. The methylation levels of <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> were significantly higher in UGC samples than those in control subjects. The sensitivities of <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> alone for UGC detection were 32.3%, 61.3% and 30.6%, respectively; when three markers were combined, the sensitivity was improved to 71.0%, with a specificity of 90.0%, and the area under the curve (AUC) was 0.870 (95% CI: 0.832–0.902). Conclusion: Methylated <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> were specific for UGC and the three-methylated gene panel provided an alternative non-invasive choice for UGC early detection.
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spelling doaj.art-698a50ebe48b4bfe8834cf93d93d40be2023-11-24T04:01:58ZengMDPI AGCancers2072-66942022-10-011421528210.3390/cancers14215282A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early DetectionCheng Peng0Guodong Zhao1Bing Pei2Kai Wang3Hui Li4Sujuan Fei5Lishuang Song6Chunkai Wang7Shangmin Xiong8Ying Xue9Qibin He10Minxue Zheng11Department of Gastroenterology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, ChinaZhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan 215300, ChinaDepartment of Clinical Laboratory, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian 223800, ChinaDepartment of R&D, Suzhou VersaBio Technologies Co. Ltd., Kunshan 215300, ChinaDepartment of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, ChinaDepartment of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, ChinaDepartment of R&D, Suzhou VersaBio Technologies Co. Ltd., Kunshan 215300, ChinaDepartment of R&D, Suzhou VersaBio Technologies Co. Ltd., Kunshan 215300, ChinaZhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan 215300, ChinaCenter for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, ChinaDepartment of Gastroenterology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, ChinaZhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan 215300, ChinaBackground: Upper gastrointestinal cancer (UGC) is an important cause of cancer death in China, with low five-year survival rates due to the majority of UGC patients being diagnosed at an advanced stage. Therefore, there is an urgent need to develop cost-effective, reliable and non-invasive methods for the early detection of UGC. Methods: A novel plasma-based methylation panel combining simultaneous detection of three methylated biomarkers (<i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i>) and an internal control gene were developed and used to examine plasma samples from 186 UGC patients and 190 control subjects. Results: The results indicated excellent PCR amplification efficiency and reproducibility of <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> in the range of 10–100,000 copies per PCR reaction of fully methylated genomic DNA. The methylation levels of <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> were significantly higher in UGC samples than those in control subjects. The sensitivities of <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> alone for UGC detection were 32.3%, 61.3% and 30.6%, respectively; when three markers were combined, the sensitivity was improved to 71.0%, with a specificity of 90.0%, and the area under the curve (AUC) was 0.870 (95% CI: 0.832–0.902). Conclusion: Methylated <i>ELMO1</i>, <i>ZNF582</i> and <i>TFPI2</i> were specific for UGC and the three-methylated gene panel provided an alternative non-invasive choice for UGC early detection.https://www.mdpi.com/2072-6694/14/21/5282upper gastrointestinal cancerDNA methylationplasmapanelearly detection
spellingShingle Cheng Peng
Guodong Zhao
Bing Pei
Kai Wang
Hui Li
Sujuan Fei
Lishuang Song
Chunkai Wang
Shangmin Xiong
Ying Xue
Qibin He
Minxue Zheng
A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection
Cancers
upper gastrointestinal cancer
DNA methylation
plasma
panel
early detection
title A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection
title_full A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection
title_fullStr A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection
title_full_unstemmed A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection
title_short A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection
title_sort novel plasma based methylation panel for upper gastrointestinal cancer early detection
topic upper gastrointestinal cancer
DNA methylation
plasma
panel
early detection
url https://www.mdpi.com/2072-6694/14/21/5282
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