A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection

Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnib...

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Main Authors: Chunxiao Bu, Zhilong Wang, Xianping Lv, Yanteng Zhao
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Epigenetics
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Online Access:https://www.tandfonline.com/doi/10.1080/15592294.2024.2374988
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author Chunxiao Bu
Zhilong Wang
Xianping Lv
Yanteng Zhao
author_facet Chunxiao Bu
Zhilong Wang
Xianping Lv
Yanteng Zhao
author_sort Chunxiao Bu
collection DOAJ
description Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2−ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4–1 and IRF4–2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4–1 and IRF4–2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.
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spelling doaj-art-8d840833536a42e8ac5ee46d73b6e09c2024-12-09T07:21:36ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2024.2374988A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detectionChunxiao Bu0Zhilong Wang1Xianping Lv2Yanteng Zhao3Department of Magnetic Resonance Imaging,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaHenan Academy of Medical Sciences, Zhengzhou, Henan, ChinaDepartment of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaEarly detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2−ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4–1 and IRF4–2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4–1 and IRF4–2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.https://www.tandfonline.com/doi/10.1080/15592294.2024.2374988Gastric cancer detectionmethylated DNA markercfDNAplasmareal-time methylated-specific PCRIRF4
spellingShingle Chunxiao Bu
Zhilong Wang
Xianping Lv
Yanteng Zhao
A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection
Epigenetics
Gastric cancer detection
methylated DNA marker
cfDNA
plasma
real-time methylated-specific PCR
IRF4
title A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection
title_full A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection
title_fullStr A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection
title_full_unstemmed A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection
title_short A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection
title_sort dual gene panel of two fragments of methylated irf4 and one of zeb2 in plasma cell free dna for gastric cancer detection
topic Gastric cancer detection
methylated DNA marker
cfDNA
plasma
real-time methylated-specific PCR
IRF4
url https://www.tandfonline.com/doi/10.1080/15592294.2024.2374988
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