Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.
Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.
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DOI：
10.3389/fcvm.2021.774755
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发表时间：
2021
影响因子：
3.6
通讯作者：
Peng L
中科院分区：
文献类型：
--
作者：
Liu X;Xu S;Li Y;Chen Q;Zhang Y;Peng L
背景：炎症激活和免疫渗透在心力衰竭的病理过程中起着重要作用。本研究旨在探讨缺血性心肌病所致心力衰竭患者的免疫渗透及相关生物标志物。方法：从基因表达总表(GEO)数据库中下载缺血性心肌病(CM)和非心力衰竭(NF)患者心力衰竭的基因表达数据。鉴定了CM和NF样本之间的差异表达基因(DEG)。单样本基因集浓缩分析(SsGSEA)用于探索免疫渗透的格局。应用加权基因共表达网络分析(WGCNA)筛选与免疫渗透相关的模块。用受试者工作曲线(ROC)曲线评价候选基因的诊断价值。分析10例CM和10例NF患者外周血单个核细胞(PBMC)中潜在生物标志物的mRNA水平，以进一步评价其诊断价值。结果：在GSE5406的CM和NF样品中共鉴定出224个DEG，主要集中在蛋白质加工和细胞外基质相关的生物学过程和途径中。SSGSEA分析结果显示，CM患者外周血中树突状细胞(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)和辅助性T细胞(Th2)的丰度明显高于正常对照组，而嗜酸性粒细胞和中央记忆T细胞(Tcm)的表达明显低于正常对照组。相关分析显示，Calumenin(CALU)、PALLD与DC、NK CD56dim细胞、T细胞、Tfh、TGD、Th2细胞丰度呈负相关，与中医证候水平呈正相关。更重要的是，CM患者PBMC的CALU和PALLD显著低于NF患者。结论：CALU和PALLD可能是缺血性心肌病心衰免疫渗透相关的潜在生物标志物。
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.
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影响因子：
10.8
作者：
de Lucia C;Grisanti LA;Borghetti G;Piedepalumbo M;Ibetti J;Lucchese AM;Barr EW;Roy R;Okyere AD;Murphy HC;Gao E;Rengo G;Houser SR;Tilley DG;Koch WJ
通讯作者：
Koch WJ
影响因子：
20.1
作者：
Luo M;Anderson ME
通讯作者：
Anderson ME
影响因子：
24
作者：
Cunningham, Jonathan W.;Claggett, Brian L.;Zile, Michael R.
通讯作者：
Zile, Michael R.
影响因子：
3.3
作者：
Mori, Masaki;Nakagami, Hironori;Kaneda, Yasufumi
通讯作者：
Kaneda, Yasufumi
影响因子：
10.8
作者：
Abplanalp, Wesley T.;John, David;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie