Exploring novel biomarkers in dilated cardiomyopathy-induced heart failure by integrated analysis and in vitro experiments

Despite the availability of several effective and promising treatment methods, heart failure (HF) remains a significant public health concern that requires advanced therapeutic strategies and techniques. Dilated cardiomyopathy (DCM) is a crucial factor that contributes to the development and deterioration of HF. The aim of the present study was to identify novel biomarkers and biological pathways to enhance the diagnosis and treatment of patients with DCM-induced HF using weighted gene co-expression network analysis (WGCNA). A total of 24 co-expressed gene modules connected with DCM-induced HF were obtained by WGCNA. Among these, the blue module had the highest correlation with DCM-induced HF (r=0.91; P<0.001) and was enriched in the AGE-RAGE signaling pathway in diabetic complications, the p53 and MAPK signaling pathway, adrenergic signaling in cardiomyocytes, the Janus kinase-STAT signaling pathway and cGMP/PKG signaling. Eight key genes, including secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2), serpin family A member 3 (SERPINA3), myosin heavy chain 6 (MYH6), S100 calcium binding protein A9 (S100A9), tubulin alpha (TUBA)3E, TUBA3D, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) and phospholipase C epsilon 1 (PLCE1), were selected as the therapeutic targets of DCM-induced HF based on WGCNA and differentially expressed gene analysis. Immune cell infiltration analysis revealed that the proportion of naive B cells and CD4-activated memory T cells was markedly upregulated in DCM-induced HF tissues compared with tissues from healthy controls. Furthermore, reverse transcription-quantitative PCR in AC16 human cardiomyocyte cells treated with doxorubicin showed that among the eight key genes, only SERPINA3, MYH6, S100A9, LYVE1 and PLCE1 exhibited expression levels identical to those revealed by bioinformatics analysis, suggesting that these genes may be involved in the development of DCM-induced HF.

Automated summary

In this study, weighted gene co-expression network analysis (WGCNA) was used to identify novel biomarkers and biological pathways for the diagnosis and treatment of dilated cardiomyopathy (DCM)-induced heart failure (HF). Through WGCNA, 24 co-expressed gene modules associated with DCM-induced HF were obtained, and the blue module showed the highest correlation with DCM-induced HF and was enriched in multiple signaling pathways. Eight key genes were selected as therapeutic targets for DCM-induced HF based on WGCNA and differentially expressed gene analysis. Immune cell infiltration analysis revealed upregulated proportions of naive B cells and CD4-activated memory T cells in DCM-induced HF tissues. Reverse transcription-quantitative PCR validated the expression levels of five key genes identified by bioinformatics analysis, suggesting their involvement in the development of DCM-induced HF.