Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression
Abstract Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been estab...
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| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-70455-x |
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| author | Lu Lu Mingjie Chen Guicheng Zhang Yujing Liu Xiangyuan Xu Zenghua Jiang Yangxian Xu Tao Liu Fan Yang Guang Ji Hanchen Xu |
| author_facet | Lu Lu Mingjie Chen Guicheng Zhang Yujing Liu Xiangyuan Xu Zenghua Jiang Yangxian Xu Tao Liu Fan Yang Guang Ji Hanchen Xu |
| author_sort | Lu Lu |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been established, their specific roles in CRC formation remain unclear. Using Circle-Sequencing and whole transcriptomic sequencing, we comprehensively profile circular DNAs and transcriptomes in healthy individuals, colorectal adenoma, and CRC patients. Our delineate analyses characterize the key circular DNAs involved in oncogene expression through the normal-adenoma–carcinoma continuum and highlight that immune response-related pathways and cell cycle pathways, are the dominat events in CRC progression. Notably, chr8 ecDNA 64950741–114379093 exhibits robust up-regulation during CRC progression. Further validation in a new cohort of 50 CRC patients confirms the higher expression of chr8 ecDNA 64950741–114379093 and its strong correlation with poor prognosis. Thus, these findings provide unprecedented insights into the landscape of circular DNAs in CRC and highlights the potential of chr8 ecDNA 64950741–114379093 as a promising biomarker and therapeutic target for CRC management. |
| format | Article |
| id | doaj-art-84bc24c4fa6a48dfb7367862464a546c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-84bc24c4fa6a48dfb7367862464a546c2024-11-24T12:26:06ZengNature PortfolioScientific Reports2045-23222024-11-0114111210.1038/s41598-024-70455-xComprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progressionLu Lu0Mingjie Chen1Guicheng Zhang2Yujing Liu3Xiangyuan Xu4Zenghua Jiang5Yangxian Xu6Tao Liu7Fan Yang8Guang Ji9Hanchen Xu10China-Canada Center of Research for Digestive Diseases (ccCRDD), Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineShanghai NewCore Biotechnology Co.LtdShanghai NewCore Biotechnology Co.LtdChina-Canada Center of Research for Digestive Diseases (ccCRDD), Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineChina-Canada Center of Research for Digestive Diseases (ccCRDD), Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Gastrointestinal Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineShanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer TransformationEndoscopy Center, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of MedicineChina-Canada Center of Research for Digestive Diseases (ccCRDD), Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineChina-Canada Center of Research for Digestive Diseases (ccCRDD), Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineAbstract Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been established, their specific roles in CRC formation remain unclear. Using Circle-Sequencing and whole transcriptomic sequencing, we comprehensively profile circular DNAs and transcriptomes in healthy individuals, colorectal adenoma, and CRC patients. Our delineate analyses characterize the key circular DNAs involved in oncogene expression through the normal-adenoma–carcinoma continuum and highlight that immune response-related pathways and cell cycle pathways, are the dominat events in CRC progression. Notably, chr8 ecDNA 64950741–114379093 exhibits robust up-regulation during CRC progression. Further validation in a new cohort of 50 CRC patients confirms the higher expression of chr8 ecDNA 64950741–114379093 and its strong correlation with poor prognosis. Thus, these findings provide unprecedented insights into the landscape of circular DNAs in CRC and highlights the potential of chr8 ecDNA 64950741–114379093 as a promising biomarker and therapeutic target for CRC management.https://doi.org/10.1038/s41598-024-70455-xCircular DNAschr8 ecDNA 64950741–114379093CRC progressionBiomarker |
| spellingShingle | Lu Lu Mingjie Chen Guicheng Zhang Yujing Liu Xiangyuan Xu Zenghua Jiang Yangxian Xu Tao Liu Fan Yang Guang Ji Hanchen Xu Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression Scientific Reports Circular DNAs chr8 ecDNA 64950741–114379093 CRC progression Biomarker |
| title | Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression |
| title_full | Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression |
| title_fullStr | Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression |
| title_full_unstemmed | Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression |
| title_short | Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression |
| title_sort | comprehensive profiling of extrachromosomal circular dnas in colorectal cancer progression |
| topic | Circular DNAs chr8 ecDNA 64950741–114379093 CRC progression Biomarker |
| url | https://doi.org/10.1038/s41598-024-70455-x |
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