Role of Oxidative Stress-Related Gene and Immune cell Infiltration in Chronic Heart Failure: Novel Insights from Bioinformatic Analyses

Abstract Background Oxidative stress and immune cells infiltration have been shown to play a role in chronic heart failure (CHF). In this study, we aimed to explore oxidative stress status and immune cells infiltration associated with CHF and they may identify new candidates for biomarker. Methods CHF samples were collected from Gene Expression Omnibus (GEO) database (GSE5406, GSE9128, and GSE76701). Differentially expressed genes of oxidative stress (OSDEGs) were identified based on differentially expressed genes (DEGs) and oxidative stress gene set. Multiple machine learning methods were adopted to screen signature OSDEGs. Consensus clustering was used to divide samples into categories with different OSDEGs levels. Functional enrichment analysis was conducted to evaluate the gene enrichment signaling pathways in OSDEGs. The correlation between OSDEGs and immune cells infiltration was performed by single sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Results Overall, 33 differentially expressed oxidative stress-related genes were identified. Among them, 10 were further regarded as independent predictors for CHF, and used to develop a nomogram that had shown good performance in predicting CHF with an area under the receiver operating characteristic curve of 0.93(95%CI: 0.85-1.00) in the training sets and 0.81 (95%CI: 0.43-1.00) in the validation set. Furthermore, hub genes were mainly enriched in the detoxification of reactive oxygen species pathway, cell redox homeostasis and negative regulation of oxidative stress-induced cell death. The CHF and control samples showed significantly different distributions (P < 0.05) of monocytes and M0 macrophages. In addition, both AKT1 and NOS3 held a positive relationship with monocytes, but HSP90AA1 was negatively correlated with natural killer cells and type 1 T helper cells, respectively. Conclusions These results indicate that oxidative stress status is closely linked to CHF risk prediction and immune cell infiltration. Thus, the oxidative stress-based molecular signature may be target for CHF intervention.