Screening and validation of key genes for ferroptosis in doxorubicin-induced cardiomyopathy on machine learning
10.12007/j.issn.0258-4646.2025.01.007
- VernacularTitle:基于机器学习筛选阿霉素诱导的心肌病中铁死亡的关键基因与验证
- Author:
Xiaoying ZENG
1
;
Xi ZHU
;
Mengting DENG
;
Zhiqiang DING
;
Hongcheng FANG
;
Yuhong DOU
Author Information
1. 广州中医药大学深圳中西医结合临床医学院,广东 深圳 518104
- Publication Type:Journal Article
- Keywords:
doxorubicin-induced cardiomyopathy;
ferroptosis;
bioinformatics;
gene
- From:
Journal of China Medical University
2025;54(1):38-43
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of ferroptosis in DIC through bioinformatics analysis of hub genes involved in ferroptosis in doxorubicin-induced cardiomyopathy(DIC),combined with in vitro experimental validation.Methods Divalent iron fluorescence staining confirms the occurrence of ferroptosis in myocardial cells of DIC.The GSE207737 dataset was retrieved from the Gene Expression Comprehensive Database(GEO)and intersected with the FerrDb database to identify ferroptosis-related genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the intersected genes and intersecting the genes obtained from LASSO regression analysis and SVM-SFR machine learning methods were used to obtain ferroptosis hub genes for DIC.Real-time PCR was used to validate H9C2 cells in the control and DIC model groups,and Western blotting was used to further validate those whose bioinformatics and real-time PCR results that did not match.Results Thirty-eight ferroptosis-related genes in DIC were identified,and GO and KEGG analyses showed that these genes mainly participate in cell metabolism.Five hub genes for ferroptosis in DIC were obtained using machine learning methods:Mpc1,Prdx1,Kdm4a,Alox 12b,and Tfrc.Through in vitro experiments,the mRNA expression levels of Mpc1,Prdx1,and Kdm4a were downregulated in the DIC model group compared to those in the control group(P＜0.001),whereas the mRNA expression level of Alox12b was upregulated(P＜0.001).There were no significant differences in the mRNA or protein expression levels of Tfrc(P＞0.05).Conclusion Mpc1,Prdx1,Kdm4a,and Alox12b are key genes involved in ferroptosis in doxorubicin-induced cardiomyopathy and potential targets for the prevention and treatment of doxorubicin-induced cardiomyopathy in ferroptosis.
