{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:05:51Z","timestamp":1790867151935,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82022043"],"award-info":[{"award-number":["82022043"]}]},{"name":"National Natural Science Foundation of China","award":["2019RU050"],"award-info":[{"award-number":["2019RU050"]}]},{"name":"National Natural Science Foundation of China","award":["2022YFA1303600"],"award-info":[{"award-number":["2022YFA1303600"]}]},{"name":"National Natural Science Foundation of China","award":["GWVI-11.2-XD27"],"award-info":[{"award-number":["GWVI-11.2-XD27"]}]},{"name":"Research Unit of Bench and Clinic Research for Liver cancer Recurrence and Metastasis, Chinese Academy of Medical Sciences","award":["82022043"],"award-info":[{"award-number":["82022043"]}]},{"name":"Research Unit of Bench and Clinic Research for Liver cancer Recurrence and Metastasis, Chinese Academy of Medical Sciences","award":["2019RU050"],"award-info":[{"award-number":["2019RU050"]}]},{"name":"Research Unit of Bench and Clinic Research for Liver cancer Recurrence and Metastasis, Chinese Academy of Medical Sciences","award":["2022YFA1303600"],"award-info":[{"award-number":["2022YFA1303600"]}]},{"name":"Research Unit of Bench and Clinic Research for Liver cancer Recurrence and Metastasis, Chinese Academy of Medical Sciences","award":["GWVI-11.2-XD27"],"award-info":[{"award-number":["GWVI-11.2-XD27"]}]},{"name":"National Key R&amp;D Program of China","award":["82022043"],"award-info":[{"award-number":["82022043"]}]},{"name":"National Key R&amp;D Program of China","award":["2019RU050"],"award-info":[{"award-number":["2019RU050"]}]},{"name":"National Key R&amp;D Program of China","award":["2022YFA1303600"],"award-info":[{"award-number":["2022YFA1303600"]}]},{"name":"National Key R&amp;D Program of China","award":["GWVI-11.2-XD27"],"award-info":[{"award-number":["GWVI-11.2-XD27"]}]},{"name":"Shanghai Municipal Health Commission","award":["82022043"],"award-info":[{"award-number":["82022043"]}]},{"name":"Shanghai Municipal Health Commission","award":["2019RU050"],"award-info":[{"award-number":["2019RU050"]}]},{"name":"Shanghai Municipal Health Commission","award":["2022YFA1303600"],"award-info":[{"award-number":["2022YFA1303600"]}]},{"name":"Shanghai Municipal Health Commission","award":["GWVI-11.2-XD27"],"award-info":[{"award-number":["GWVI-11.2-XD27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) develops through multiple mechanisms. While recent studies have shown the presence of extrachromosomal circular DNA (eccDNA) in most cancer types, the eccDNA expression pattern and its association with HCC remain obscure. We aimed to investigate this problem. The genome-wide eccDNA profiles of eight paired HCC and adjacent non-tumor tissue samples were comprehensively elucidated based on Circle-seq, and they were further cross-analyzed with the RNA sequencing data to determine the association between eccDNA expression and transcriptome dysregulation. A total of 60,423 unique eccDNA types were identified. Most of the detected eccDNAs were smaller than 1 kb, with a length up to 182,363 bp and a mean sizes of 674 bp (non-tumor) and 813 bp (tumor), showing a greater association with gene-rich rather than with gene-poor regions. Although there was no statistical difference in length and chromosome distribution, the eccDNA patterns between HCC and adjacent non-tumor tissues showed significant differences at both the chromosomal and single gene levels. Five of the eight HCC tissues showed significantly higher amounts of chromosome 22-derived eccDNA expression compared to the non-tumor tissue. Furthermore, two genes, SLC16A3 and BAIAP2L2, with a higher transcription level in tumor tissues, were related to eccDNAs exclusively detected in three HCC samples and were negatively associated with survival rates in HCC cohorts from public databases. These results indicate the existence and massive heterogeneity of eccDNAs in HCC and adjacent liver tissues, and suggest their potential association with dysregulated gene expression.<\/jats:p>","DOI":"10.3390\/cancers15225309","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:25:31Z","timestamp":1699356331000},"page":"5309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genome-Wide Extrachromosomal Circular DNA Profiling of Paired Hepatocellular Carcinoma and Adjacent Liver Tissues"],"prefix":"10.3390","volume":"15","author":[{"given":"Jianyu","family":"Ye","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE & NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Huang","sequence":"additional","affiliation":[{"name":"Liver Cancer Institute, Fudan University, Shanghai 200032, China"},{"name":"Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE & NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE & NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Hua","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE & NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2550-331X","authenticated-orcid":false,"given":"Wenjing","family":"Zai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE & NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-0239","authenticated-orcid":false,"given":"Jieliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE & NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiutao","family":"Fu","sequence":"additional","affiliation":[{"name":"Liver Cancer Institute, Fudan University, Shanghai 200032, China"},{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Llovet, J.M., Kelley, R.K., Villanueva, A., Singal, A.G., Pikarsky, E., Roayaie, S., and Lencioni, R. 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