Exploring novel biomarkers in dilated cardiomyopathy‑induced heart failure by integrated analysis and <em>in vitro</em> experiments

Zhou,Lei; Zhou,Lei; Zhou,Lei; Peng,Fei; Peng,Fei; Peng,Fei; Li,Juexing; Li,Juexing; Li,Juexing; Gong,Hui; Gong,Hui; Gong,Hui

doi:10.3892/etm.2023.12024

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

Authors:
- Lei Zhou
- Fei Peng
- Juexing Li
- Hui Gong
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Affiliations: Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
Published online on: May 16, 2023 https://doi.org/10.3892/etm.2023.12024
Article Number: 325
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 α (TUBA)3E, TUBA3D, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) and phospholipase C ε1 (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.

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