Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke.
Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke.
复制标题
基于染色质调节因子的缺血性中风免疫生物标志物的实验验证和验证
DOI：
10.3389/fgene.2022.992847
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发表时间：
2022
影响因子：
3.7
通讯作者：
Gong, Shouping
中科院分区：
文献类型：
--
作者：
Yu, Beibei;Tian, Yunze;Zhang, Yongfeng;Lv, Boqiang;Li, Jianzhong;Gong, Shouping
缺血性卒中（IS）是一种进展迅速、死亡率和致残率高的疾病。其病理生理过程与免疫功能紊乱密不可分。最近，染色质调节因子（CR）已被描述为一类酶，可以识别，形成和维持生物体的表观遗传状态，并与免疫调节密切相关。然而，CR相关基因在IS中的作用尚未完全阐明。本研究通过结合差异基因表达分析、加权相关网络分析和单样本基因集富集分析，在GSE 58294和GSE 22255数据集中鉴定了7个CR相关免疫生物标志物。在使用定量聚合酶链反应进行实验验证后，筛选了四个基因（DPF2、LMNB 1、MLLT 3和JAK2）作为候选免疫生物标志物。这四种生物标志物在临床风险模型中表现出良好的预测能力（曲线下面积，0.775）。分子对接模拟显示，美伐他汀、WP 1066、克拉屈滨、阿司他汀A、美喹他嗪和祖氯米芬可能是IS的潜在免疫调节药物。总之，本研究结果有助于确定IS中CR相关的免疫治疗靶点，并为进一步研究提供重要参考。
Ischemic stroke (IS) is a disease characterized by rapid progression and high mortality and disability rates. Its pathophysiological process is inseparable from immune dysfunction. Recently, chromatin regulators (CRs) have been described as a class of enzymes that can recognize, form, and maintain the epigenetic state of an organism, and are closely associated with immune regulation. Nevertheless, the role of CR-related genes in IS has not been fully elucidated. In this study, seven CR-related immune biomarkers in the GSE58294 and GSE22255 datasets were identified by combining differential gene expression analysis, weighted correlation network analysis, and single sample gene set enrichment analysis. After experimental validation using quantitative polymerase chain reaction, four genes (DPF2, LMNB1, MLLT3, and JAK2) were screened as candidate immune biomarkers. These four biomarkers demonstrated good predictive power in the clinical risk model (area under the curve, 0.775). Molecular docking simulations revealed that mevastatin, WP1066, cladribine, trichostatin A, mequitazine, and zuclomiphene may be potential immunomodulatory drugs for IS. Overall, the results of this study contribute to the identification of CR-related immune therapeutics target in IS and provide an important reference for further research.
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DOI：
10.3390/ijerph18147552
发表时间：
2021-07-15
影响因子：
--
作者：
Rochmah TN;Rahmawati IT;Dahlui M;Budiarto W;Bilqis N
通讯作者：
Bilqis N
影响因子：
4.8
作者：
Wang X;Wang Q;Wang K;Ni Q;Li H;Su Z;Xu Y
通讯作者：
Xu Y
影响因子：
6.3
作者：
Krug, Tiago;Gabriel, Joao Paulo;Oliveira, Sofia A.
通讯作者：
Oliveira, Sofia A.
影响因子：
7
作者：
Li, Ping;Shi, Dong-Ping;Jin, Tao;Tang, Dong;Wang, Wei;Wang, Liu-Hua
通讯作者：
Wang, Liu-Hua
影响因子：
5.8
作者：
Yoo, Minjae;Shin, Jimin;Tan, Aik Choon
通讯作者：
Tan, Aik Choon