Three ER Stress Genes Flagged as Candidate Biomarkers for Heart Muscle Disease

Researchers have identified three genes linked to endoplasmic reticulum stress that may serve as candidate feature genes in hypertrophic cardiomyopathy, a condition in which the heart muscle thickens and can impair heart function.

Endoplasmic reticulum stress is a cellular mechanism that helps maintain homeostasis, and it has been implicated in the development of hypertrophic cardiomyopathy. The research team set out to find genes connected to both this stress response and the disease itself, hoping to offer new perspectives and potential targets for future heart disease treatments.

From this pipeline, three genes emerged: FKBP5, MYH6 and PROS1. The team also built a transcriptomic classification nomogram based on these genes, which showed favorable internal apparent performance with an area under the curve of 0.974.

Beyond gene selection, the study examined the immune landscape of the disease. Using the CIBERSORT algorithm, the researchers calculated the proportions of infiltrating immune cells and found that eight types of immune cells were significantly changed in hypertrophic cardiomyopathy. Monocytes showed a significant correlation with both FKBP5 and PROS1.

Single-cell RNA-sequencing analysis added another layer of detail, revealing that PROS1 was localized to cardiomyocytes within myocardial specimens from patients with the condition. This localization suggests the gene’s expression pattern within the heart muscle itself rather than in infiltrating cell populations.

The expression trends of MYH6 and PROS1 in this model were consistent with the results of the bioinformatics analysis, providing experimental support for the computational findings.

According to the authors, the study identified three endoplasmic reticulum stress-associated candidate feature genes in hypertrophic cardiomyopathy that showed a significant correlation with immune cells. They state that the findings provide a theoretical basis and reference value for exploring the relationship between the disease, ER stress and immunity.

As with any bioinformatics-driven study, the diagnostic model’s reported performance reflects internal validation, and the experimental verification was conducted in a cell model of induced hypertrophy rather than in patients. The authors describe the identified genes as candidate feature genes, positioning the work as a foundation for further research into how endoplasmic reticulum stress and immune activity intersect in this heart muscle disease.

Subject of Research: Identification of endoplasmic reticulum stress-related feature genes in hypertrophic cardiomyopathy using bioinformatics and experimental verification.

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

Article References: Tian, Z., Zhao, F., Mou, H., Wei, X., & Wang, Y. (2026). Selection of endoplasmic reticulum stress-related feature genes in hypertrophic cardiomyopathy based on bioinformatics analysis and experimental verification. BMC Medical Genomics. https://doi.org/10.1186/s12920-026-02507-2

Image Credits: AI Generated

DOI: 10.1186/s12920-026-02507-2

Keywords: hypertrophic cardiomyopathy, endoplasmic reticulum stress, FKBP5, MYH6, PROS1, bioinformatics, WGCNA, machine learning, CIBERSORT, single-cell RNA sequencing, RT-qPCR, nomogram