Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures
Abstract Background Extrachromosomal circular DNA (eccDNA) is crucial for carcinogenesis and bile has direct contact with malignant biliary strictures, yet eccDNA features in bile and its function in malignant biliary strictures remain underexplored. Results We observed the widespread presence of ec...
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BMC
2025-02-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-025-01361-6 |
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| author | Zhuo Cheng Xuanmei Luo Wenzheng Liu Xiaofang Lu Hong Chang Yingchun Wang Wei Zheng Xiue Yan Yonghui Huang |
| author_facet | Zhuo Cheng Xuanmei Luo Wenzheng Liu Xiaofang Lu Hong Chang Yingchun Wang Wei Zheng Xiue Yan Yonghui Huang |
| author_sort | Zhuo Cheng |
| collection | DOAJ |
| description | Abstract Background Extrachromosomal circular DNA (eccDNA) is crucial for carcinogenesis and bile has direct contact with malignant biliary strictures, yet eccDNA features in bile and its function in malignant biliary strictures remain underexplored. Results We observed the widespread presence of eccDNA in bile and systematically profiled the landscape of bile cell-free eccDNA (bcf-eccDNA). For functional exploration, a simple and efficient workflow was designed to synthesize large eccDNA particularly containing multiple regions. Compared with the noncancer group, bcf-eccDNAs in the cancer group had different origins and larger sizes with six characteristic peaks. These peaks were also identified in the validation cohort (100%). There were more bcf-eccDNA carrying LINC00598 or CELF2 in malignant biliary strictures, showing potential diagnostic performance in training and validation cohorts (all AUCs > 0.9). Bcf-eccDNAs carried cancer-related mutations, which could guide treatment. EccDNA carrying miR-106a/363 cluster or miR-374b/421 cluster were proven to regulate cancer gene expression, accelerate tumor proliferation, and inhibit tumor apoptosis. Conclusions This study profiles a comprehensive bcf-eccDNA landscape in patients with biliary strictures and offers valuable insights into eccDNA's role in bile liquid biopsy and carcinogenesis. |
| format | Article |
| id | doaj-art-57498b64577e4e2f97314c5f970b9453 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Cell & Bioscience |
| spelling | doaj-art-57498b64577e4e2f97314c5f970b94532025-02-09T12:56:19ZengBMCCell & Bioscience2045-37012025-02-0115111410.1186/s13578-025-01361-6Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary stricturesZhuo Cheng0Xuanmei Luo1Wenzheng Liu2Xiaofang Lu3Hong Chang4Yingchun Wang5Wei Zheng6Xiue Yan7Yonghui Huang8Department of Gastroenterology and Hepatology, Peking University Third HospitalPeking University Fifth School of Clinical MedicineDepartment of Gastroenterology and Hepatology, Peking University Third HospitalDepartment of Gastroenterology, Beijing Tsinghua Changgung HospitalDepartment of Gastroenterology and Hepatology, Peking University Third HospitalDepartment of Gastroenterology and Hepatology, Peking University Third HospitalDepartment of Gastroenterology and Hepatology, Peking University Third HospitalDepartment of Gastroenterology, Beijing Tsinghua Changgung HospitalDepartment of Gastroenterology and Hepatology, Peking University Third HospitalAbstract Background Extrachromosomal circular DNA (eccDNA) is crucial for carcinogenesis and bile has direct contact with malignant biliary strictures, yet eccDNA features in bile and its function in malignant biliary strictures remain underexplored. Results We observed the widespread presence of eccDNA in bile and systematically profiled the landscape of bile cell-free eccDNA (bcf-eccDNA). For functional exploration, a simple and efficient workflow was designed to synthesize large eccDNA particularly containing multiple regions. Compared with the noncancer group, bcf-eccDNAs in the cancer group had different origins and larger sizes with six characteristic peaks. These peaks were also identified in the validation cohort (100%). There were more bcf-eccDNA carrying LINC00598 or CELF2 in malignant biliary strictures, showing potential diagnostic performance in training and validation cohorts (all AUCs > 0.9). Bcf-eccDNAs carried cancer-related mutations, which could guide treatment. EccDNA carrying miR-106a/363 cluster or miR-374b/421 cluster were proven to regulate cancer gene expression, accelerate tumor proliferation, and inhibit tumor apoptosis. Conclusions This study profiles a comprehensive bcf-eccDNA landscape in patients with biliary strictures and offers valuable insights into eccDNA's role in bile liquid biopsy and carcinogenesis.https://doi.org/10.1186/s13578-025-01361-6Malignant biliary stricturesBile cell-free extrachromosomal circular DNADiagnostic biomarkersLiquid biopsy assayNanopore sequencingCarcinogenesis |
| spellingShingle | Zhuo Cheng Xuanmei Luo Wenzheng Liu Xiaofang Lu Hong Chang Yingchun Wang Wei Zheng Xiue Yan Yonghui Huang Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures Cell & Bioscience Malignant biliary strictures Bile cell-free extrachromosomal circular DNA Diagnostic biomarkers Liquid biopsy assay Nanopore sequencing Carcinogenesis |
| title | Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures |
| title_full | Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures |
| title_fullStr | Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures |
| title_full_unstemmed | Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures |
| title_short | Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures |
| title_sort | comprehensive landscape and oncogenic role of extrachromosomal circular dna in malignant biliary strictures |
| topic | Malignant biliary strictures Bile cell-free extrachromosomal circular DNA Diagnostic biomarkers Liquid biopsy assay Nanopore sequencing Carcinogenesis |
| url | https://doi.org/10.1186/s13578-025-01361-6 |
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