Identification of diagnostic biomarkers and therapeutic targets in peripheral immune landscape from coronary artery disease

小桶 免疫系统 冠状动脉疾病 计算生物学 疾病 医学 基因 生物信息学 生物 免疫学 内科学 基因表达 转录组 遗传学
作者
Xiaoteng Feng,Yifan Zhang,Min Du,Sijin Li,Jie Ding,Jiarou Wang,Yiru Wang,Ping Liu
出处
期刊:Journal of Translational Medicine [BioMed Central]
卷期号:20 (1) 被引量:21
标识
DOI:10.1186/s12967-022-03614-1
摘要

Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD.We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis.A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR-/- mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-β, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway.We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
小白完成签到,获得积分10
2秒前
科隆龙完成签到,获得积分10
6秒前
DAYTOY完成签到,获得积分10
8秒前
zx完成签到,获得积分20
9秒前
在水一方应助方法采纳,获得10
9秒前
Ava应助孙成成采纳,获得30
10秒前
凡迪亚比应助lena采纳,获得10
13秒前
14秒前
14秒前
香蕉觅云应助zcy采纳,获得10
16秒前
NexusExplorer应助科研通管家采纳,获得10
17秒前
田様应助科研通管家采纳,获得10
17秒前
未命名应助科研通管家采纳,获得20
17秒前
lant0932应助科研通管家采纳,获得10
17秒前
Lyla应助科研通管家采纳,获得10
17秒前
俏皮诺言发布了新的文献求助10
17秒前
JamesPei应助科研通管家采纳,获得10
18秒前
无花果应助科研通管家采纳,获得10
18秒前
传奇3应助科研通管家采纳,获得10
18秒前
AGuang应助科研通管家采纳,获得10
18秒前
Ava应助科研通管家采纳,获得10
18秒前
大模型应助科研通管家采纳,获得10
18秒前
领导范儿应助科研通管家采纳,获得10
18秒前
桐桐应助科研通管家采纳,获得30
18秒前
逸之狐应助科研通管家采纳,获得20
18秒前
香蕉觅云应助科研通管家采纳,获得10
18秒前
19秒前
23秒前
seal发布了新的文献求助10
25秒前
myduty完成签到 ,获得积分10
25秒前
123完成签到,获得积分10
25秒前
26秒前
26秒前
老实雁蓉完成签到,获得积分10
28秒前
28秒前
Brian发布了新的文献求助10
28秒前
28秒前
28秒前
寒江雪举报起名求助涉嫌违规
30秒前
洞幺拐发布了新的文献求助10
30秒前
高分求助中
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Cognitive Neuroscience: The Biology of the Mind (Sixth Edition) 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 588
Christian Women in Chinese Society: The Anglican Story 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3961083
求助须知:如何正确求助?哪些是违规求助? 3507362
关于积分的说明 11135734
捐赠科研通 3239863
什么是DOI,文献DOI怎么找? 1790434
邀请新用户注册赠送积分活动 872400
科研通“疑难数据库(出版商)”最低求助积分说明 803150