南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (5): 859-866.doi: 10.12122/j.issn.1673-4254.2024.05.07
收稿日期:
2023-10-26
出版日期:
2024-05-20
发布日期:
2024-06-06
通讯作者:
张大发
E-mail:welson1987@163.com;zhangdafa2256@126.com
作者简介:
周 伟,博士,主治医师,E-mail: welson1987@163.com
基金资助:
Wei ZHOU1(), Jun NIE1, Jia HU2, Yizhi JIANG3, Dafa ZHANG1(
)
Received:
2023-10-26
Online:
2024-05-20
Published:
2024-06-06
Contact:
Dafa ZHANG
E-mail:welson1987@163.com;zhangdafa2256@126.com
Supported by:
摘要:
目的 探讨内质网应激相关基因(ERSAGs)在主动脉夹层疾病(AD)中的差异性表达及免疫浸润相关性,为AD的治疗寻找新的靶点。 方法 检索GEO数据库,下载GSE190635及GSE98770两个主动脉夹层mRNA数据集,R软件分析AD患者主动脉与正常主动脉差异表达基因(DEGs),从GeneCards网站下载ERSAGs基因集。GeneMANIA数据库分析内质网应激(ERS)差异基因晚期糖基化终末产物受体(AGER)相互作用的蛋白。基于GSE98770数据集使用R语言CIBERSORT包计算AD患者主动脉壁组织内22种免疫细胞分布比例。临床收集20例主动脉壁标本,分为AD组和非AD组(n=10/组),qRT-PCR检测AGER表达量。使用TRRUST数据库和NetworkAnalyst数据库分析预测AGER上游转录因子、miRNA及调控作用化合物。 结果 获取到ERS差异基因AGER,与其相互作用的蛋白共有20种,主要生物功能:模式识别受体信号通路,DNA结合转录因子活性的正向调节,骨髓白细胞迁移,白细胞迁移,调节I-kappaB激酶/NF-kappaB信号传导。AD中AEGR表达水平与Treg细胞丰度间呈正相关(r=0.59,P<0.05)。qRT-PCR检测显示,AD组主动脉壁AGER表达量为1.00±0.30,非AD组表达量为1.76±0.68,差异具有统计学意义(P<0.05)。ROC曲线分析显示,AGER预测AD的AUC=0.86(95% CI:0.67~1.00,P=0.0073),cut-off值为1.335,对应的敏感性和特异性分别为80%、90%。AGER调控网络预测到3种转录因子,3种miRNAs,27种化合物。 结论 内质网应激相关基因AGER在主动脉夹层疾病中的低表达,其可能通过Treg细胞影响AD的发生。
周伟, 聂军, 胡佳, 蒋艺枝, 张大发. 内质网应激相关基因在主动脉夹层疾病中的差异性表达及与免疫浸润的相关性[J]. 南方医科大学学报, 2024, 44(5): 859-866.
Wei ZHOU, Jun NIE, Jia HU, Yizhi JIANG, Dafa ZHANG. Differential expressions of endoplasmic reticulum stress-associated genes in aortic dissection and their correlation with immune cell infiltration[J]. Journal of Southern Medical University, 2024, 44(5): 859-866.
Primers | Sequence (5'-3') |
---|---|
β-Actin | F:AGCGAGCATCCCCCAAAGTT; R:GGGCACGAAGGCTCATCATT |
AGER | F: GTGTCCTTCCCAACGGCTC; R: ATTGCCTGGCACCGGAAAA |
表1 qRT-PCR引物序列
Tab.1 Primer sequences for qRT-PCR
Primers | Sequence (5'-3') |
---|---|
β-Actin | F:AGCGAGCATCCCCCAAAGTT; R:GGGCACGAAGGCTCATCATT |
AGER | F: GTGTCCTTCCCAACGGCTC; R: ATTGCCTGGCACCGGAAAA |
图1 AD差异表达基因
Fig.1 Differentially expressed genes (DEGs) in AD. A: Volcano plot of the DEGs in GSE190635. Red points represent up-regulated genes, and blue points represent down-regulated genes; Black points represent genes without significant difference (NS). B: Heatmap of DEGs in GSE190635. C: Volcano plot for the DEGs in GSE98770. D: Heatmap of the DEGs in GSE98770.
图4 免疫细胞浸润分析
Fig.4 Immune cell infiltration analysis in the aorta of AD patients. A: CIBERSORT algorithm-based topography of the 22 immune cells in AD samples in GSE98770 dataset. B: Correlation analysis of the 22 immune cells. C: Correlation analysis of AGER with the 22 immune cells. D: Correlation analysis between Treg cell percentage and AGER expression level. Pearson method, *P<0.05.
图5 主动脉临床标本验证
Fig.5 Validation of AGER mRNA expression in clinical aorta specimens. A: qRT-PCR detection of AGER expression in AD and NAD groups. B: ROC curve analysis. **P<0.01.
TF | Target | Type | PMID |
---|---|---|---|
NFKB1 | AGER | Activation | 18622638;19616578 |
PPARG | AGER | Repression | 18855759 |
RELA | AGER | Activation | 18622638;19616578 |
表2 AGER转录因子
Tab.2 Transcriptional factors (TF) of AGER
TF | Target | Type | PMID |
---|---|---|---|
NFKB1 | AGER | Activation | 18622638;19616578 |
PPARG | AGER | Repression | 18855759 |
RELA | AGER | Activation | 18622638;19616578 |
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