Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer
As one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free...
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.596078/full |
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| author | Shengyue Li Lei Wang Qiang Zhao Zhihao Wang Shuxian Lu Yani Kang Gang Jin Jing Tian |
| author_facet | Shengyue Li Lei Wang Qiang Zhao Zhihao Wang Shuxian Lu Yani Kang Gang Jin Jing Tian |
| author_sort | Shengyue Li |
| collection | DOAJ |
| description | As one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free DNA (cfDNA) methylation in plasma has attracted global attention for non-invasive and early cancer diagnosis. Here, we carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (p-value < 0.0001). Then, 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. After performing the least absolute shrinkage and selection operator (LASSO) method, a total of eight markers were found to fairly distinguish PDAC patients from healthy individuals, including TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977, and LOC100130148. In conclusion, this work identified a set of eight differentially methylated markers that may be potentially applied in non-invasive diagnosis of pancreatic cancer. |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-23T23:25:11Z |
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| series | Frontiers in Genetics |
| spelling | doaj.art-06bb8209e0994c60b4205c75d6a906f72022-12-21T17:26:14ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-12-011110.3389/fgene.2020.596078596078Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic CancerShengyue Li0Lei Wang1Qiang Zhao2Zhihao Wang3Shuxian Lu4Yani Kang5Gang Jin6Jing Tian7Key laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi’an, ChinaDepartment of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, ChinaSchool of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai, ChinaKey laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi’an, ChinaKey laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi’an, ChinaSchool of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, ChinaKey laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi’an, ChinaAs one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free DNA (cfDNA) methylation in plasma has attracted global attention for non-invasive and early cancer diagnosis. Here, we carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (p-value < 0.0001). Then, 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. After performing the least absolute shrinkage and selection operator (LASSO) method, a total of eight markers were found to fairly distinguish PDAC patients from healthy individuals, including TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977, and LOC100130148. In conclusion, this work identified a set of eight differentially methylated markers that may be potentially applied in non-invasive diagnosis of pancreatic cancer.https://www.frontiersin.org/articles/10.3389/fgene.2020.596078/fullpancreatic ductal adenocarcinomacfDNAMeDIP-seqmethylationbiomarkers |
| spellingShingle | Shengyue Li Lei Wang Qiang Zhao Zhihao Wang Shuxian Lu Yani Kang Gang Jin Jing Tian Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer Frontiers in Genetics pancreatic ductal adenocarcinoma cfDNA MeDIP-seq methylation biomarkers |
| title | Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer |
| title_full | Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer |
| title_fullStr | Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer |
| title_full_unstemmed | Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer |
| title_short | Genome-Wide Analysis of Cell-Free DNA Methylation Profiling for the Early Diagnosis of Pancreatic Cancer |
| title_sort | genome wide analysis of cell free dna methylation profiling for the early diagnosis of pancreatic cancer |
| topic | pancreatic ductal adenocarcinoma cfDNA MeDIP-seq methylation biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.596078/full |
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