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Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure
Frontiers in Cardiovascular Medicine ( IF 3.6 ) Pub Date : 2021-12-01 , DOI: 10.3389/fcvm.2021.774755
Xing Liu 1 , Shiyue Xu 2 , Ying Li 3 , Qian Chen 1 , Yuanyuan Zhang 1 , Long Peng 1
Affiliation  

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.

Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.

Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.

Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.



中文翻译:

鉴定 CALU 和 PARLD 作为与心力衰竭免疫浸润相关的潜在生物标志物

背景:炎症激活和免疫浸润在心力衰竭 (HF) 的病理过程中起重要作用。目前的研究旨在调查缺血性心肌病导致的心力衰竭患者的免疫浸润并确定相关生物标志物。

方法:从基因表达综合 (GEO) 数据库下载缺血性心肌病 (CM) 样本和非心力衰竭 (NF) 样本导致的 HF 表达数据。鉴定了 CM 和 NF 样品之间的差异表达基因 (DEG)。进行单样本基因集富集分析 (ssGSEA) 以探索免疫浸润的景观。应用加权基因共表达网络分析 (WGCNA) 来筛选与免疫浸润相关的最相关模块。通过受试者工作曲线(ROC)曲线评估候选基因的诊断价值。分析了从 10 名 CM 患者和 10 名 NF 患者中分离出的外周血单核细胞 (PBMC) 中潜在生物标志物的 mRNA 水平,以进一步评估其诊断价值。

结果:GSE5406中CM和NF样品共鉴定出224个DEGs,主要富集在蛋白质加工和细胞外基质相关的生物过程和途径中。ssGSEA 的结果显示树突状细胞 (DC)、肥大细胞、自然杀伤 (NK) CD56dim 细胞、T 细胞、T 滤泡辅助细胞 (Tfh)、gammadelta T 细胞 (Tgd) 和 T 辅助细胞 2 (Th2) 的丰度细胞显着更高,而与 NF 样品相比,CM 样品中嗜酸性粒细胞和中枢记忆 T 细胞 (Tcm) 的浸润较低。相关性分析显示,Calumenin(CALU)和palladin(PALLD)与DC、NK CD56dim细胞、T细胞、Tfh、Tgd和Th2细胞丰度呈负相关,与Tcm水平呈正相关。更重要的是,

结论: 我们的研究表明,CALU 和 PARLD 是与缺血性心肌病引起的心力衰竭的免疫浸润相关的潜在生物标志物。

更新日期:2021-12-01
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