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缺血性心肌病炎症相关基因潜在生物标志物的鉴定。

Identification of potential biomarkers of inflammation-related genes for ischemic cardiomyopathy.

作者信息

Wang Jianru, Xie Shiyang, Cheng Yanling, Li Xiaohui, Chen Jian, Zhu Mingjun

机构信息

Department of Cardiovascular, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

Central Laboratory, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Front Cardiovasc Med. 2022 Aug 23;9:972274. doi: 10.3389/fcvm.2022.972274. eCollection 2022.

Abstract

OBJECTIVE

Inflammation plays an important role in the pathophysiology of ischemic cardiomyopathy (ICM). We aimed to identify potential biomarkers of inflammation-related genes for ICM and build a model based on the potential biomarkers for the diagnosis of ICM.

MATERIALS AND METHODS

The microarray datasets and RNA-Sequencing datasets of human ICM were downloaded from the Gene Expression Omnibus database. We integrated 8 microarray datasets the SVA package to screen the differentially expressed genes (DEGs) between ICM and non-failing control samples, then the differentially expressed inflammation-related genes (DEIRGs) were identified. The least absolute shrinkage and selection operator, support vector machine recursive feature elimination, and random forest were utilized to screen the potential diagnostic biomarkers from the DEIRGs. The potential biomarkers were validated in the RNA-Sequencing datasets and the functional experiment of the ICM rat, respectively. A nomogram was established based on the potential biomarkers and evaluated the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), and Clinical impact curve (CIC).

RESULTS

64 DEGs and 19 DEIRGs were identified, respectively. 5 potential biomarkers (SERPINA3, FCN3, PTN, CD163, and SCUBE2) were ultimately selected. The validation results showed that each of these five potential biomarkers showed good discriminant power for ICM, and their expression trends were consistent with the bioinformatics results. The results of AUC, calibration curve, DCA, and CIC showed that the nomogram demonstrated good performance, calibration, and clinical utility.

CONCLUSION

SERPINA3, FCN3, PTN, CD163, and SCUBE2 were identified as potential biomarkers associated with the inflammatory response to ICM. The proposed nomogram could potentially provide clinicians with a helpful tool to the diagnosis and treatment of ICM from an inflammatory perspective.

摘要

目的

炎症在缺血性心肌病(ICM)的病理生理学中起重要作用。我们旨在识别ICM炎症相关基因的潜在生物标志物,并基于这些潜在生物标志物构建一个用于诊断ICM的模型。

材料与方法

从基因表达综合数据库下载人类ICM的微阵列数据集和RNA测序数据集。我们使用SVA软件包整合8个微阵列数据集,以筛选ICM与非衰竭对照样本之间的差异表达基因(DEGs),然后识别差异表达的炎症相关基因(DEIRGs)。利用最小绝对收缩和选择算子、支持向量机递归特征消除和随机森林从DEIRGs中筛选潜在的诊断生物标志物。分别在RNA测序数据集和ICM大鼠功能实验中验证潜在生物标志物。基于潜在生物标志物建立列线图,并通过受试者操作特征曲线(AUC)下面积、校准曲线、决策曲线分析(DCA)和临床影响曲线(CIC)进行评估。

结果

分别识别出64个DEGs和19个DEIRGs。最终选择了5个潜在生物标志物(丝氨酸蛋白酶抑制剂A3、甘露糖结合凝集素3、多效生长因子、CD163和信号肽CUB域含蛋白2)。验证结果表明,这五个潜在生物标志物中的每一个对ICM都具有良好的判别能力,并且它们的表达趋势与生物信息学结果一致。AUC、校准曲线、DCA和CIC的结果表明,列线图具有良好的性能、校准和临床实用性。

结论

丝氨酸蛋白酶抑制剂A3、甘露糖结合凝集素3、多效生长因子、CD163和信号肽CUB域含蛋白2被确定为与ICM炎症反应相关的潜在生物标志物。所提出的列线图可能为临床医生从炎症角度诊断和治疗ICM提供一个有用的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/9445158/3c49f959c97b/fcvm-09-972274-g001.jpg

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