Targeting ERBB2 and PIK3R1 as a therapeutic strategy for dilated cardiomyopathy: A single-cell sequencing and...

Area of Science:

• Genomics and Bioinformatics
• Cardiovascular Research
• Oncology

Background:

• Dilated cardiomyopathy (DCM) is a major cause of heart failure.
• Current pharmaceutical options for DCM lack disease-modifying capabilities.
• Novel therapeutic targets are urgently needed for DCM treatment.

Purpose of the Study:

• To identify drug-treatable genes associated with dilated cardiomyopathy (DCM).
• To investigate the causal relationship between identified genes and heart failure.
• To explore the role of these genes in immune response and potential therapeutic interventions.

Main Methods:

• Utilized big data analysis and bioinformatics to evaluate gene sets (SC-DCM, EP-DCM, Drug).
• Employed microarray datasets to validate gene expression and discriminatory power.
• Conducted Mendelian randomization and DGIdb analysis to assess causality and identify targeted drugs.

Main Results:

• Identified PIK3R1 and ERBB2 as key drug-treatable genes in DCM.
• Confirmed a causal association between ERBB2 and heart failure; PIK3R1 showed no causal link.
• PIK3R1 correlated positively with immune activation, while ERBB2 showed negative correlation; Everolimus inhibits both.

Conclusions:

• PIK3R1 and ERBB2 are viable therapeutic targets for DCM.
• ERBB2 may protect against DCM progression to heart failure.
• Cross-expression of PIK3R1 and ERBB2 in DCM and tumors suggests shared pathways and potential for repurposed therapies.