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基于机器学习的 Stanford A 型主动脉夹层中与铁死亡相关生物标志物的鉴定

Identification of ferroptosis-associated biomarkers in Stanford type A aortic dissection based on machine learning.

作者信息

Pan Hao, Lu Wei, Liu Zhifei, Wang Yu

机构信息

Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan, Shandong, China.

Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan, Shandong, China.

出版信息

Am J Transl Res. 2023 May 15;15(5):3092-3114. eCollection 2023.

Abstract

BACKGROUND

Stanford type A aortic dissection (STAAD) is a serious cardiovascular disease with a high mortality rate. Ferroptosis is closely associated with various diseases, including cardiovascular disease. However, the role of ferroptosis in the progression of STAAD remains unclear.

METHODS

Gene expression profiles of GSE52093, GSE98770, and GSE153434 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and support vector machine-recursive feature elimination (SVM-RFE) were performed to determine the ferroptosis-associated characteristic genes in STAAD. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy. Furthermore, immune cell infiltrations were analyzed using the CIBERSORT algorithm. Drug sensitivity analysis was conducted based on the CellMiner database.

RESULTS

A total of 65 differentially expressed ferroptosis-associated genes were screened. DAZAP1 and GABARAPL2 were identified as valuable diagnostic biomarkers for STAAD. A nomogram with high accuracy and reliability was constructed as a diagnostic tool for STAAD. Furthermore, immune infiltration analysis suggested that monocytes were higher in the STAAD group compared with the control group. DAZAP1 was positively correlated with monocytes, whereas GABARAPL2 was negatively correlated with monocytes. Pan-cancer analysis showed that DAZAP1 and GABARAPL2 were closely associated with the prognosis of various cancers. In addition, some antitumor drugs might be useful for the treatment of STAAD.

CONCLUSION

DAZAP1 and GABARAPL2 might serve as potential diagnostic biomarkers for STAAD. Meanwhile, DAZAP1 and GABARAPL2 might be related to cancer and STAAD in terms of ferroptosis, which provides insights into developing new therapeutic approaches for STAAD.

摘要

背景

A型主动脉夹层(STAAD)是一种严重的心血管疾病,死亡率很高。铁死亡与包括心血管疾病在内的多种疾病密切相关。然而,铁死亡在STAAD进展中的作用仍不清楚。

方法

从基因表达综合数据库(GEO)下载GSE52093、GSE98770和GSE153434数据集的基因表达谱。进行加权基因共表达网络分析(WGCNA)、最小绝对收缩和选择算子(LASSO)以及支持向量机递归特征消除(SVM-RFE)以确定STAAD中铁死亡相关的特征基因。进行受试者工作特征(ROC)曲线分析以评估诊断效能。此外,使用CIBERSORT算法分析免疫细胞浸润。基于CellMiner数据库进行药物敏感性分析。

结果

共筛选出65个差异表达的铁死亡相关基因。DAZAP1和GABARAPL2被确定为STAAD有价值的诊断生物标志物。构建了一个具有高准确性和可靠性的列线图作为STAAD的诊断工具。此外,免疫浸润分析表明,STAAD组的单核细胞比对照组更高。DAZAP1与单核细胞呈正相关,而GABARAPL2与单核细胞呈负相关。泛癌分析表明,DAZAP1和GABARAPL2与多种癌症的预后密切相关。此外,一些抗肿瘤药物可能对STAAD的治疗有用。

结论

DAZAP1和GABARAPL2可能作为STAAD的潜在诊断生物标志物。同时,DAZAP1和GABARAPL2在铁死亡方面可能与癌症和STAAD相关,这为开发STAAD的新治疗方法提供了思路。

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