5-Hydroxymethylcytosine in circulating cell-free DNA as a potential diagnostic biomarker for SLE

doi:10.1136/lupus-2024-001286

科研成果详情

题名	5-Hydroxymethylcytosine in circulating cell-free DNA as a potential diagnostic biomarker for SLE
作者	Tong, Xinya 1; Chen, Wenwen 1; Ye, Lele 2; Xiong, Yanling3; Xu, Yuan 1; Luo, Yunhui1; Xia, Xinhang1; Xu, Zexia3; Lin, Yutong 4; Zhu, Xinqi 4; Wang, Nan 1; Xue, Xiangyang1; Zhang, Huidi3; Guo, Gangqiang1
发表日期	2024-10-04
发表期刊	Lupus Science and Medicine 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Autoimmune Diseases Lupus Erythematosus, Systemic Autoimmunity
其他关键词	LUPUS ; 5HMC ; NEPHROPATHY ; SIGNATURES ; BINDING
摘要	Background SLE is a complex autoimmune disease with heterogeneous manifestations and unpredictable outcomes. Early diagnosis is challenging due to non-specific symptoms, and current treatments only manage symptoms. Epigenetic alternations, including 5-Hydroxymethylome (5hmC) modifications, are important contributors to SLE pathogenesis. However, the 5hmC modification status in circulating cell-free DNA (cfDNA) of patients with SLE remains largely unexplored. We investigated the distribution of 5hmC in cfDNA of patients with SLE and healthy controls (HCs), and explored its potential as an SLE diagnosis marker.Methods We used 5hmC-Seal to generate genome-wide 5hmC profiles of plasma cfDNA and bioinformatics analysis to screen differentially hydroxymethylated regions (DhMRs). In vitro mechanistic exploration was conducted to investigate the regulatory effect of CCCTC-binding factor (CTCF) in 5hmC candidate biomarkers.Results We found distinct differences in genomic regions and 5hmC modification motif patterns between patients with SLE and HCs, varying with disease progression. Increased 5hmC modification enrichment was detected in SLE. Additionally, we screened 151 genes with hyper-5hmC, which are significantly involved in SLE-related processes, and 5hmC-modified BCL2, CD83, ETS1 and GZMB as SLE biomarkers. Our findings suggest that CTCF regulates 5hmC modification of these genes by recruiting TET (ten-eleven translocation) protein, and CTCF knockdown affected the protein expression of these genes in vitro.Conclusions Our findings demonstrate the increased 5hmC distribution in plasma cfDNA in different disease activity in patients with SLE compared with HCs and relating DhMRs involved in SLE-associated pathways. Furthermore, we identified a panel of SLE relevant biomarkers, and these viewpoints could provide insight into the pathogenesis of SLE.
资助项目	National Natural Science Foundation of China [32200476, 82001705]; Zhejiang Provincial Natural Science Foundation of China [LQ23C060002]; Wenzhou Municipal Science and Technology Bureau [Y20220044]
出版者	BMJ PUBLISHING GROUP
ISSN	2053-8790
卷号	11 期号:2
DOI	10.1136/lupus-2024-001286
页数	15
WOS类目	Rheumatology
WOS研究方向	Rheumatology
WOS记录号	WOS:001328581700001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39366755
SCOPUSEID	2-s2.0-85206526708
通讯作者地址	[Xue, Xiangyang;Guo, Gangqiang]Wenzhou Med Univ, Inst Mol Virol & Immunol, Inst Trop Med, Sch Basic Med Sci,Dept Microbiol & Immunol,Wenzhou, Wenzhou, Zhejiang, Peoples R China. ; [Zhang, Huidi]Wenzhou Med Univ, Affiliated Hosp 1, Dept Nephrol, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Rheumatology;Immunology
SCOPUS_ID	SCOPUS_ID:85206526708
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220712
专题	基础医学院（机能实验教学中心）_病原生物学与免疫学系第一临床医学院（信息与工程学院）、附属第一医院附属第一医院_妇科附属第一医院_肾内科
通讯作者	Xue, Xiangyang; Zhang, Huidi; Guo, Gangqiang
作者单位	1.Wenzhou Med Univ, Inst Mol Virol & Immunol, Inst Trop Med, Sch Basic Med Sci,Dept Microbiol & Immunol,Wenzhou, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Dept Gynecol, Wenzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 1, Dept Nephrol, Wenzhou, Zhejiang, Peoples R China; 4.Wenzhou Med Univ, Clin Coll 1, Wenzhou, Zhejiang, Peoples R China
第一作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系; 附属第一医院_肾内科
第一作者的第一单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
推荐引用方式 GB/T 7714	Tong, Xinya,Chen, Wenwen,Ye, Lele,et al. 5-Hydroxymethylcytosine in circulating cell-free DNA as a potential diagnostic biomarker for SLE[J]. Lupus Science and Medicine,2024,11(2).
APA	Tong, Xinya., Chen, Wenwen., Ye, Lele., Xiong, Yanling., Xu, Yuan., ... & Guo, Gangqiang. (2024). 5-Hydroxymethylcytosine in circulating cell-free DNA as a potential diagnostic biomarker for SLE. Lupus Science and Medicine, 11(2).
MLA	Tong, Xinya,et al."5-Hydroxymethylcytosine in circulating cell-free DNA as a potential diagnostic biomarker for SLE".Lupus Science and Medicine 11.2(2024).