Abstract：
BACKGROUND: Dilated cardiomyopathy (DCM) is a complex type of cardiomyopathy that is affected by both genetic and non-genetic factors. It is characterized by an enlargement of the left ventricle or bi-ventricle, and is often accompanied by cardiac systolic dysfunction. The main results include arrhythmia, heart failure (HF), and sudden death. The prognosis of this disease is usually poor, and the 5-year survival time is about 50%. Early diagnosis is very important for the treatment of DCM. Studies have shown that primary prevention after discovering the disease effectively reduces the mortality rate of the disease. However, there is currently no effective biomarker for the early diagnosis of DCM. The rapid development of omics in protein has promoted the \"precise\" study of modern medical research. In this article, the potential biomarkers for predicting and diagnosing DCM-related HF were studied by a plasma protein omics analysis.
METHODS: Tandem mass tag-labeled quantitative proteomic studies were performed in 20 patients, comprising 10 DCM-associated HF patients, and 10 control patients who without clinical HF events. Further validation research was conducted by enzyme-linked immunosorbent assay (ELISA) with an expanded cohort (control group =40; HF group =48).
RESULTS: Among the 854 identified proteins, the expression of 86 proteins was significantly upregulated, while the expression of 21 proteins was downregulated (with an expression difference >1.5-fold; P<0.05) in the 2 groups. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction (PPI) networks analyses indicated that the bicarbonate transport process played a critical role in HF. Importantly, carbonic anhydrase 2 (CA2) and 3 (CA3), which play central roles in regulating the transport of bicarbonate, were highly expressed in the HF group. The ELISA validation results showed that the expression levels of CA2 and CA3 at admission were remarkably higher (P<0.0001 and P=0.0157) in the plasma of the HF patients than that of the control patients.
CONCLUSIONS: The present study showed that two molecules (i.e., CA2 and CA3) are involved in the bicarbonate transport pathway, and are risk factors and potential biomarkers for the diagnosis of DCM patients with HF.
METHODS: Tandem mass tag-labeled quantitative proteomic studies were performed in 20 patients, comprising 10 DCM-associated HF patients, and 10 control patients who without clinical HF events. Further validation research was conducted by enzyme-linked immunosorbent assay (ELISA) with an expanded cohort (control group =40; HF group =48).
RESULTS: Among the 854 identified proteins, the expression of 86 proteins was significantly upregulated, while the expression of 21 proteins was downregulated (with an expression difference >1.5-fold; P<0.05) in the 2 groups. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction (PPI) networks analyses indicated that the bicarbonate transport process played a critical role in HF. Importantly, carbonic anhydrase 2 (CA2) and 3 (CA3), which play central roles in regulating the transport of bicarbonate, were highly expressed in the HF group. The ELISA validation results showed that the expression levels of CA2 and CA3 at admission were remarkably higher (P<0.0001 and P=0.0157) in the plasma of the HF patients than that of the control patients.
CONCLUSIONS: The present study showed that two molecules (i.e., CA2 and CA3) are involved in the bicarbonate transport pathway, and are risk factors and potential biomarkers for the diagnosis of DCM patients with HF.
摘要：
背景：扩张型心肌病（DCM）是一种复杂类型的心肌病，受遗传和非遗传因素的影响。它的特征是左心室或双心室扩大，常伴有心脏收缩功能障碍。主要结果包括心律失常，心力衰竭(HF),突然死亡。这种疾病的预后通常较差，5年生存时间约为50%。早期诊断对DCM的治疗非常重要。研究表明，发现疾病后的一级预防有效降低了疾病的死亡率。然而,目前尚无有效的早期诊断DCM的生物标志物。蛋白质组学的快速发展促进了现代医学研究的“精确”研究。在这篇文章中,通过血浆蛋白质组学分析研究了预测和诊断DCM相关HF的潜在生物标志物.
方法：对20例患者进行了串联质量标签标记的定量蛋白质组学研究，包括10名DCM相关的HF患者，和10名没有临床HF事件的对照患者。通过酶联免疫吸附测定（ELISA）与扩展队列（对照组=40；HF组=48）进行进一步的验证研究。
结果：在854个鉴定的蛋白质中，86种蛋白质的表达显著上调,而两组中21种蛋白表达下调（表达差异>1.5倍；P<0.05）。基因本体论,京都基因和基因组途径富集百科全书，和蛋白质-蛋白质相互作用（PPI）网络分析表明，碳酸氢盐转运过程在HF中起关键作用。重要的是,碳酸酐酶2（CA2）和3（CA3），在调节碳酸氢盐的运输中起着核心作用，在HF组中高表达。ELISA验证结果显示，HF患者入院时血浆中CA2和CA3的表达水平明显高于对照组（P<0.0001和P=0.0157）。
结论：本研究表明，两个分子(即，CA2和CA3）参与碳酸氢盐转运途径，并且是诊断DCM伴HF患者的危险因素和潜在生物标志物。
方法：对20例患者进行了串联质量标签标记的定量蛋白质组学研究，包括10名DCM相关的HF患者，和10名没有临床HF事件的对照患者。通过酶联免疫吸附测定（ELISA）与扩展队列（对照组=40；HF组=48）进行进一步的验证研究。
结果：在854个鉴定的蛋白质中，86种蛋白质的表达显著上调,而两组中21种蛋白表达下调（表达差异>1.5倍；P<0.05）。基因本体论,京都基因和基因组途径富集百科全书，和蛋白质-蛋白质相互作用（PPI）网络分析表明，碳酸氢盐转运过程在HF中起关键作用。重要的是,碳酸酐酶2（CA2）和3（CA3），在调节碳酸氢盐的运输中起着核心作用，在HF组中高表达。ELISA验证结果显示，HF患者入院时血浆中CA2和CA3的表达水平明显高于对照组（P<0.0001和P=0.0157）。
结论：本研究表明，两个分子(即，CA2和CA3）参与碳酸氢盐转运途径，并且是诊断DCM伴HF患者的危险因素和潜在生物标志物。
