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铁代谢相关基因揭示急性冠状动脉综合征的预测价值。

Iron metabolism-related genes reveal predictive value of acute coronary syndrome.

作者信息

Xu Cong, Li Wanyang, Li Tangzhiming, Yuan Jie, Pang Xinli, Liu Tao, Liang Benhui, Cheng Lixin, Sun Xin, Dong Shaohong

机构信息

Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University, Shenzhen, China.

School of Mathematics, South China University of Technology, Guangzhou, China.

出版信息

Front Pharmacol. 2022 Oct 18;13:1040845. doi: 10.3389/fphar.2022.1040845. eCollection 2022.

Abstract

Iron deficiency has detrimental effects in patients with acute coronary syndrome (ACS), which is a common nutritional disorder and inflammation-related disease affects up to one-third people worldwide. However, the specific role of iron metabolism in ACS progression is opaque. In this study, we construct an iron metabolism-related genes (IMRGs) based molecular signature of ACS and to identify novel iron metabolism gene markers for early stage of ACS. The IMRGs were mainly collected from Molecular Signatures Database (mSigDB) and two relevant studies. Two blood transcriptome datasets GSE61144 and GSE60993 were used for constructing the prediction model of ACS. After differential analysis, 22 IMRGs were differentially expressed and defined as DEIGs in the training set. Then, the 22 DEIGs were trained by the Elastic Net to build the prediction model. Five genes, PADI4, HLA-DQA1, LCN2, CD7, and VNN1, were determined using multiple Elastic Net calculations and retained to obtain the optimal performance. Finally, the generated model iron metabolism-related gene signature (imSig) was assessed by the validation set GSE60993 using a series of evaluation measurements. Compared with other machine learning methods, the performance of imSig using Elastic Net was superior in the validation set. Elastic Net consistently scores the higher than Lasso and Logistic regression in the validation set in terms of ROC, PRC, Sensitivity, and Specificity. The prediction model based on iron metabolism-related genes may assist in ACS early diagnosis.

摘要

缺铁对急性冠状动脉综合征(ACS)患者有不利影响,急性冠状动脉综合征是一种常见的营养失调和炎症相关疾病,全球多达三分之一的人受其影响。然而,铁代谢在急性冠状动脉综合征进展中的具体作用尚不清楚。在本研究中,我们构建了基于铁代谢相关基因(IMRGs)的急性冠状动脉综合征分子特征,并鉴定急性冠状动脉综合征早期的新型铁代谢基因标志物。铁代谢相关基因主要从分子特征数据库(mSigDB)和两项相关研究中收集。使用两个血液转录组数据集GSE61144和GSE60993构建急性冠状动脉综合征的预测模型。经过差异分析,在训练集中有22个铁代谢相关基因差异表达并定义为差异表达铁代谢相关基因(DEIGs)。然后,通过弹性网络对这22个差异表达铁代谢相关基因进行训练以构建预测模型。通过多次弹性网络计算确定了五个基因,即肽基精氨酸脱亚氨酶4(PADI4)、人白细胞抗原DQA1(HLA-DQA1)、脂质运载蛋白2(LCN2)、CD7和钒依赖性核苷酸焦磷酸酶/磷酸二酯酶1(VNN1),并保留这些基因以获得最佳性能。最后,使用一系列评估指标,通过验证集GSE60993对生成的模型铁代谢相关基因特征(imSig)进行评估。与其他机器学习方法相比,弹性网络生成的imSig在验证集中性能更优。在验证集中,就受试者工作特征曲线(ROC)、精确召回率曲线(PRC)、敏感性和特异性而言,弹性网络的得分始终高于套索回归和逻辑回归。基于铁代谢相关基因的预测模型可能有助于急性冠状动脉综合征的早期诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0445/9622999/ecd1364154aa/fphar-13-1040845-g001.jpg

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