Selection of endoplasmic reticulum stress-related feature genes in hypertrophic cardiomyopathy based on bioinformatics analysis and experimental verification

Endoplasmic reticulum stress (ERS) is a crucial mechanism for maintaining cellular homeostasis and plays a significant role in the pathogenesis of hypertrophic cardiomyopathy (HCM). Identifying ERS-associated feature genes related to HCM and ERS can provide new perspectives and potential targets for future treatments of heart diseases. Multiple datasets were downloaded from the GEO database, followed by differential analysis and weighted gene co-expression network analysis (WGCNA) to screen genes most related to HCM. ERS-related genes were intersected with the previously identified genes. Feature genes were screened using machine learning methods, diagnostic efficacy, and expression validation, and a nomogram was constructed based on the feature genes. The CIBERSORT algorithm was used to calculate the proportion of immune cell infiltration, and single-cell RNA-sequencing analysis was used to characterize the expression of the feature gene across different cell types. Finally, the expression of the feature gene was verified by real-time quantitative PCR (RT-qPCR). FKBP5, MYH6 and PROS1 were regarded as feature genes. The transcriptomic classification nomogram model constructed based on these genes shows favorable internal apparent performance (AUC = 0.974). Immune analysis revealed that 8 types of immune cells in HCM were significantly changed, and monocytes were significantly correlated with FKBP5 and PROS1. Single‑cell RNA‑sequencing analysis revealed that PROS1 was localized to cardiomyocytes within HCM myocardial specimens. RT-qPCR experiment verified that the expression trends of MYH6 and PROS1 in the Ang II-induced cardiomyocyte hypertrophy model were consistent with the results of bioinformatics analysis. This study identified three ERS‑associated candidate feature genes in HCM that showed a significant correlation with immune cells. The findings provide a theoretical basis and reference value for exploring the relationship between HCM, ER stress, and immunity.