Integrated analysis of C3AR1 and CD163 associated with immune infiltration in intracranial aneurysms pathogenesis.
Integrated analysis of C3AR1 and CD163 associated with immune infiltration in intracranial aneurysms pathogenesis.
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与颅内动脉瘤发病机理中免疫浸润有关的C3AR1和CD163的综合分析。
DOI：
10.1016/j.heliyon.2023.e14470
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发表时间：
2023-03
期刊：
影响因子：
4
通讯作者：
Zhang, Lei
中科院分区：
文献类型：
--
作者：
Li, Shengjie;Xiao, Jinting;Yu, Zaiyang;Li, Junliang;Shang, Hao;Zhang, Lei
确定颅内动脉瘤（IAs）的潜在免疫相关生物标志物、分子机制和治疗剂。我们鉴定了来自GSE75436、GSE26969、GSE6551和GSE13353数据集的IAs和对照样本之间的差异表达基因（DEGs）。我们使用加权基因共表达网络分析（WGCNA）和蛋白-蛋白相互作用（PPI）分析来鉴定免疫相关的枢纽基因。我们利用qRT-PCR分析hub基因的表达。利用miRNet、NetworkAnalyst和DGIdb数据库，我们分析了中枢基因的调控网络和潜在的治疗药物。最小绝对收缩和选择算子（LASSO）逻辑回归在中心基因中确定最佳生物标志物。通过外部GSE15629数据集验证诊断值。我们在来自GSE75436、GSE26969、GSE6551和GSE13353数据集的IAs和对照样本中鉴定出227个deg和22个差异浸润免疫细胞。我们进一步鉴定了41个差异表达的免疫相关基因（DEIRGs），这些基因主要富集于趋化因子介导的信号通路、髓系白细胞迁移、内噬泡膜、趋化因子受体结合、趋化因子活性以及病毒蛋白与细胞因子及其受体的相互作用。在41个DEIRGs中，鉴定出C3AR1、CD163、CCL4、CXCL8、CCL3、TLR2、TYROBP、C1QB、FCGR3A、FCGR1A等10个中心基因具有较好的诊断价值（AUC为0.7）。Hsa-mir-27a-3p和转录因子，包括YY1和GATA2，被确定为枢纽基因的主要调节因子。预测了92种靶向中枢基因的潜在治疗药物。采用LASSO logistic回归分析，最终确定C3AR1和CD163为最佳诊断biomarkers （AUC = 0.994）。C3AR1和CD163的诊断价值通过外部GSE15629数据集验证（AUC = 0.914）。本研究揭示了C3AR1和CD163在IAs发病机制中免疫浸润的重要作用。本研究结果为后续研究IAs的分子机制和干预的潜在靶点提供了有价值的参考。
To identify potential immune-related biomarkers, molecular mechanism, and therapeutic agents of intracranial aneurysms (IAs). We identified the differentially expressed genes (DEGs) between IAs and control samples from GSE75436, GSE26969, GSE6551, and GSE13353 datasets. We used weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) analysis to identify immune-related hub genes. We evaluated the expression of hub genes by using qRT-PCR analysis. Using miRNet, NetworkAnalyst, and DGIdb databases, we analyzed the regulatory networks and potential therapeutic agents targeting hub genes. Least absolute shrinkage and selection operator (LASSO) logistic regression was performed to identify optimal biomarkers among hub genes. The diagnostic value was validated by external GSE15629 dataset. We identified 227 DEGs and 22 differentially infiltrating immune cells between IAs and control samples from GSE75436, GSE26969, GSE6551, and GSE13353 datasets. We further identified 41 differentially expressed immune-related genes (DEIRGs), which were primarily enriched in the chemokine-mediated signaling pathway, myeloid leukocyte migration, endocytic vesicle membrane, chemokine receptor binding, chemokine activity, and viral protein interactions with cytokines and their receptors. Among 41 DEIRGs, 10 hub genes including C3AR1, CD163, CCL4, CXCL8, CCL3, TLR2, TYROBP, C1QB, FCGR3A, and FCGR1A were identified with good diagnostic values (AUC >0.7). Hsa-mir-27a-3p and transcription factors, including YY1 and GATA2, were identified the primary regulators of hub genes. 92 potential therapeutic agents targeting hub genes were predicted. C3AR1 and CD163 were finally identified as the best diagnostic biomarkers using LASSO logistic regression (AUC = 0.994). The diagnostic value of C3AR1 and CD163 was validated by the external GSE15629 dataset (AUC = 0.914). This study revealed the importance of C3AR1 and CD163 in immune infiltration in IAs pathogenesis. Our finding provided a valuable reference for subsequent research on the potential targets for molecular mechanisms and intervention of IAs.
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
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作者：
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影响因子：
48
作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.omtn.2020.09.030
发表时间：
2020-12-04
期刊：
Molecular therapy. Nucleic acids
影响因子：
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作者：
Choe N;Kwon DH;Ryu J;Shin S;Cho HJ;Joung H;Eom GH;Ahn Y;Park WJ;Nam KI;Kim YK;Kook H
通讯作者：
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