Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5‐year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor‐originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy bio...
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| Format: | Article |
| Language: | English |
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Wiley
2024-11-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13643 |
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| author | Guochao Zhao Ruijingfang Jiang Ying Shi Suizhi Gao Dansong Wang Zhilong Li Yuhong Zhou Jianlong Sun Wenchuan Wu Jiaxi Peng Tiantao Kuang Yefei Rong Jie Yuan Shida Zhu Gang Jin Yuying Wang Wenhui Lou |
| author_facet | Guochao Zhao Ruijingfang Jiang Ying Shi Suizhi Gao Dansong Wang Zhilong Li Yuhong Zhou Jianlong Sun Wenchuan Wu Jiaxi Peng Tiantao Kuang Yefei Rong Jie Yuan Shida Zhu Gang Jin Yuying Wang Wenhui Lou |
| author_sort | Guochao Zhao |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5‐year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor‐originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA‐based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer‐specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation‐based model significantly. Moreover, the combination of the methylation‐based model with carbohydrate antigen 19‐9 (CA19‐9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation‐based and integrated liquid biopsy assays hold promise as non‐invasive tools for detection of PDAC. |
| format | Article |
| id | doaj-art-b094acad6c084888b80b80a3f9b3b75d |
| institution | OA Journals |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-b094acad6c084888b80b80a3f9b3b75d2025-08-20T02:13:15ZengWileyMolecular Oncology1574-78911878-02612024-11-0118112801281310.1002/1878-0261.13643Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinomaGuochao Zhao0Ruijingfang Jiang1Ying Shi2Suizhi Gao3Dansong Wang4Zhilong Li5Yuhong Zhou6Jianlong Sun7Wenchuan Wu8Jiaxi Peng9Tiantao Kuang10Yefei Rong11Jie Yuan12Shida Zhu13Gang Jin14Yuying Wang15Wenhui Lou16Department of Pancreatic Surgery, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaEnvelope Health Biotechnology Co. Ltd., BGI‐Shenzhen ChinaEnvelope Health Biotechnology Co. Ltd., BGI‐Shenzhen ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Affiliated to Navy Medical University Shanghai ChinaDepartment of Pancreatic Surgery, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaEnvelope Health Biotechnology Co. Ltd., BGI‐Shenzhen ChinaDepartment of Medical Oncology, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaEnvelope Health Biotechnology Co. Ltd., BGI‐Shenzhen ChinaDepartment of Pancreatic Surgery, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaEnvelope Health Biotechnology Co. Ltd., BGI‐Shenzhen ChinaDepartment of Pancreatic Surgery, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Pancreatic Surgery, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaThe Fifth Affiliated Hospital of Southern Medical University Guangzhou ChinaBGI Genomics BGI‐Shenzhen ChinaDepartment of Hepatobiliary Pancreatic Surgery Changhai Hospital Affiliated to Navy Medical University Shanghai ChinaEnvelope Health Biotechnology Co. Ltd., BGI‐Shenzhen ChinaDepartment of Pancreatic Surgery, Cancer Center, Zhongshan Hospital Fudan University Shanghai ChinaPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5‐year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor‐originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA‐based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer‐specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation‐based model significantly. Moreover, the combination of the methylation‐based model with carbohydrate antigen 19‐9 (CA19‐9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation‐based and integrated liquid biopsy assays hold promise as non‐invasive tools for detection of PDAC.https://doi.org/10.1002/1878-0261.13643cfDNAliquid biopsymachine learningmethylationmutationpancreatic ductal adenocarcinoma |
| spellingShingle | Guochao Zhao Ruijingfang Jiang Ying Shi Suizhi Gao Dansong Wang Zhilong Li Yuhong Zhou Jianlong Sun Wenchuan Wu Jiaxi Peng Tiantao Kuang Yefei Rong Jie Yuan Shida Zhu Gang Jin Yuying Wang Wenhui Lou Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma Molecular Oncology cfDNA liquid biopsy machine learning methylation mutation pancreatic ductal adenocarcinoma |
| title | Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma |
| title_full | Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma |
| title_fullStr | Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma |
| title_short | Circulating cell‐free DNA methylation‐based multi‐omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma |
| title_sort | circulating cell free dna methylation based multi omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma |
| topic | cfDNA liquid biopsy machine learning methylation mutation pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1002/1878-0261.13643 |
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