Integrative analysis of bioinformatics and machine learning to identify cuprotosis-related biomarkers and immunological characteristics in heart failure

生物信息学与机器学习的综合分析以识别心力衰竭中与杯状硬化相关的生物标志物和免疫学特征

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作者:Dingyuan Tu #, Qiang Xu #, Yanmin Luan #, Jie Sun #, Xiaoli Zuo, Chaoqun Ma

Conclusions

Our study discovered that cuprotosis was strongly related to the pathogenesis of HF, probably by regulating energy metabolism-associated and immune-associated signaling pathways.

Methods

The HF microarray datasets GSE16499, GSE26887, GSE42955, GSE57338, GSE76701, and GSE79962 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed CRGs between HF patients and nonfailing donors (NFDs). Four machine learning models were used to identify key CRGs features for HF diagnosis. The expression profiles of key CRGs were further validated in a merged GEO external validation dataset and human samples through quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In addition, Gene Ontology (GO) function enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and immune infiltration analysis were used to investigate potential biological functions of key CRGs.

Results

We discovered nine differentially expressed CRGs in heart tissues from HF patients and NFDs. With the aid of four machine learning algorithms, we identified three indicators of cuprotosis (DLAT, SLC31A1, and DLST) in HF, which showed good diagnostic properties. In addition, their differential expression between HF patients and NFDs was confirmed through qRT-PCR. Moreover, the results of enrichment analyses and immune infiltration exhibited that these diagnostic markers of CRGs were strongly correlated to energy metabolism and immune activity. Conclusions: Our study discovered that cuprotosis was strongly related to the pathogenesis of HF, probably by regulating energy metabolism-associated and immune-associated signaling pathways.

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