Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients

To explore SLE staging markers, we analyzed eccDNA in plasma using circular sequencing, comparing healthy controls (HC), active SLE (ASLE), and inactive SLE (ISLE) patients. We found higher eccDNA levels and lower GC content in ASLE and ISLE compared to healthy controls, with a negative correlation...

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Main Authors: Yali Peng, Huihui Tao, Dongzhou Liu, Donger Tang, Chunmei Wen, Mengyao Wu, Tiantian Xu, Guoying Wang, Xuejia Zheng, Yong Dai
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Epigenetics
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Online Access:https://www.tandfonline.com/doi/10.1080/15592294.2025.2477903
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author Yali Peng
Huihui Tao
Dongzhou Liu
Donger Tang
Chunmei Wen
Mengyao Wu
Tiantian Xu
Guoying Wang
Xuejia Zheng
Yong Dai
author_facet Yali Peng
Huihui Tao
Dongzhou Liu
Donger Tang
Chunmei Wen
Mengyao Wu
Tiantian Xu
Guoying Wang
Xuejia Zheng
Yong Dai
author_sort Yali Peng
collection DOAJ
description To explore SLE staging markers, we analyzed eccDNA in plasma using circular sequencing, comparing healthy controls (HC), active SLE (ASLE), and inactive SLE (ISLE) patients. We found higher eccDNA levels and lower GC content in ASLE and ISLE compared to healthy controls, with a negative correlation between GC content and anti-daDNA, C3, and C4 levels in SLE and HC samples. Differential expression of exon-derived eccGenes in ASLE and ISLE suggests their role in SLE development, with KEGG analysis showing enrichment in SLE-related pathways for these differentially expressed genes. By protein–protein interactions network analysis we found 9 exon-derived eccGenes that were significantly differentially expressed and scored high in both ISLE-HC and ASLE-ISLE as diagnostic criteria for differentiating different disease stages of SLE. In conclusion, the present study reveals that eccDNA length GC content as well as chromosomal distribution in ASLE, ISLE and HC suggests that with eccDNA is associated with the creation of SLE, suggesting GC count of eccDNA as a diagnostic marker for systemic lupus erythematosus. Significant changes in the abundance of eccDNA-related genes from exons such as SOS1, GAD2, BCL11B, PPT1, and GCNT3 were observed in ISLE as compared to ASLE and HC groups and were significantly correlated with SLEDAI-2K. This suggests that these exon-derived eccGenes may play a role in the development and progression of the disease. Consequently, the abundance levels of these exon-derived eccGenes could potentially assist in distinguishing different stages of SLE, beyond a confirmed diagnosis, thus serving as possible biomarkers for the condition.
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spelling doaj-art-ed683553b2154161a58c8b1486fe2a732025-08-20T03:42:41ZengTaylor & Francis GroupEpigenetics1559-22941559-23082025-12-0120110.1080/15592294.2025.2477903Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patientsYali Peng0Huihui Tao1Dongzhou Liu2Donger Tang3Chunmei Wen4Mengyao Wu5Tiantian Xu6Guoying Wang7Xuejia Zheng8Yong Dai9School of Medicine, Anhui University of Science & Technology, Huainan, ChinaSchool of Medicine, Anhui University of Science & Technology, Huainan, ChinaGuangdong Provincial Autoimmune Disease Precision Medicine Engineering Research Center, Shenzhen Autoimmune Disease Engineering Research Center, Shenzhen Geriatrics Clinical Research Center, Shenzhen People ‘s Hospital, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, ChinaGuangdong Provincial Autoimmune Disease Precision Medicine Engineering Research Center, Shenzhen Autoimmune Disease Engineering Research Center, Shenzhen Geriatrics Clinical Research Center, Shenzhen People ‘s Hospital, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, ChinaSchool of Medicine, Anhui University of Science & Technology, Huainan, ChinaSchool of Medicine, Anhui University of Science & Technology, Huainan, ChinaSchool of Medicine, Anhui University of Science & Technology, Huainan, ChinaSchool of Medicine, Anhui University of Science & Technology, Huainan, ChinaThe First Hospital of Anhui University of Science and Technology, Huainan, ChinaSchool of Medicine, Anhui University of Science & Technology, Huainan, ChinaTo explore SLE staging markers, we analyzed eccDNA in plasma using circular sequencing, comparing healthy controls (HC), active SLE (ASLE), and inactive SLE (ISLE) patients. We found higher eccDNA levels and lower GC content in ASLE and ISLE compared to healthy controls, with a negative correlation between GC content and anti-daDNA, C3, and C4 levels in SLE and HC samples. Differential expression of exon-derived eccGenes in ASLE and ISLE suggests their role in SLE development, with KEGG analysis showing enrichment in SLE-related pathways for these differentially expressed genes. By protein–protein interactions network analysis we found 9 exon-derived eccGenes that were significantly differentially expressed and scored high in both ISLE-HC and ASLE-ISLE as diagnostic criteria for differentiating different disease stages of SLE. In conclusion, the present study reveals that eccDNA length GC content as well as chromosomal distribution in ASLE, ISLE and HC suggests that with eccDNA is associated with the creation of SLE, suggesting GC count of eccDNA as a diagnostic marker for systemic lupus erythematosus. Significant changes in the abundance of eccDNA-related genes from exons such as SOS1, GAD2, BCL11B, PPT1, and GCNT3 were observed in ISLE as compared to ASLE and HC groups and were significantly correlated with SLEDAI-2K. This suggests that these exon-derived eccGenes may play a role in the development and progression of the disease. Consequently, the abundance levels of these exon-derived eccGenes could potentially assist in distinguishing different stages of SLE, beyond a confirmed diagnosis, thus serving as possible biomarkers for the condition.https://www.tandfonline.com/doi/10.1080/15592294.2025.2477903Systemic lupus erythematosus (SLE)extrachromosomal circular DNA (eccDNA)biomarkersactive and inactive SLEdifferential expression analysiscircular sequencing
spellingShingle Yali Peng
Huihui Tao
Dongzhou Liu
Donger Tang
Chunmei Wen
Mengyao Wu
Tiantian Xu
Guoying Wang
Xuejia Zheng
Yong Dai
Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients
Epigenetics
Systemic lupus erythematosus (SLE)
extrachromosomal circular DNA (eccDNA)
biomarkers
active and inactive SLE
differential expression analysis
circular sequencing
title Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients
title_full Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients
title_fullStr Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients
title_full_unstemmed Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients
title_short Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients
title_sort comprehensive analysis of eccdna characteristics and associated genes expression in peripheral blood of asle and isle patients
topic Systemic lupus erythematosus (SLE)
extrachromosomal circular DNA (eccDNA)
biomarkers
active and inactive SLE
differential expression analysis
circular sequencing
url https://www.tandfonline.com/doi/10.1080/15592294.2025.2477903
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