The Function, Role and Process of DDX58 in Heart Failure and Human Cancers

Abstract

Background: Heart failure (HF) is the most common outcome of cardiovascular disease, and an increasing number of patients with heart failure die from noncardiac causes, such as cancer. Epidemiological data suggest that ischemic cardiomyopathy–induced HF (ischemic HF) may be associated with an increased incidence of cancer. This study aimed to investigate the possible mechanisms of the association between ischemic HF and cancer, as well as potential therapeutic targets. Methods: Weighted gene co-expression network analysis was performed to analyze the correlations between phenotypes and gene modules using immune cells as phenotypes. Differential analysis was then performed to screen differentially expressed genes (DEGs) in ischemic HF and normal control samples. The macrophage-related Brown module was identified as the key module, and immune-related DEGs were obtained by taking the intersection of the Brown module, DEGs, and immune-related genes using a Venn diagram. DDX58 was identified as the key gene using a protein–protein interaction network and expression analyses and validated using immunohistochemistry. Kaplan–Meier survival analysis was performed to analyze the correlation between DDX58 expression and tumor prognosis. Spearman correlation analysis was performed to assess the correlation between DDX58 expression and immune cell infiltration. Results: DDX58 was identified as a key immune-related gene associated with ischemic HF and was highly expressed in most cancer types. The survival analysis revealed a significant negative correlation between high DDX58 expression and prognosis in multiple tumor types. Moreover, DDX58 expression was significantly associated with immune cell infiltration and immune checkpoint gene expression in many cancer types. Conclusion: DDX58 is a key immune-related gene in ischemic HF and may play a crucial role in the relationship between ischemic HF and cancer. Pan-cancer analysis suggests that DDX58 is a promising clinical prognostic marker for most cancers and may be a therapeutic target for cancer patients and ischemic HF patients at an increased risk of cancer.