Co-Expression Transcriptomic Profiling Identifies Sex-Universal Molecular Markers of Muscle Atrophy

Abstract

Muscle disuse atrophy (MDA) is a debilitating condition caused by prolonged inactivity. Given the gender differences, mechanisms of MDA are often investigated separately for each gender. To better understand the similarities and differences between genders in MDA, we analysed transcriptomic data from the gene expression omnibus database, stratified by gender, to identify differentially expressed genes. Weighted gene co-expression network analysis was employed to construct co-expression modules and identify hub genes. Least absolute shrinkage and selection operator regression was used to select common hub genes, and their diagnostic potential was validated using ROC analysis. Additionally, immune cell infiltration analysis was performed to explore the role of immune dysregulation in MDA. This study identified that CD36 was a biomarker across genders, while C21ORF33 was a male MDA biomarker. WGCNA revealed gender-specific co-expression modules significantly correlated with MDA traits. Immune cell infiltration analysis showed upregulated immature B cells and downregulated eosinophils in female MDA, highlighting the role of immune dysregulation. CD36 and C21ORF33 demonstrated strong discriminatory power. Expression of these two biomarkers was validated in tenotomy mouse modelling. This study emphasised the roles of chronic inflammation and immune dysregulation in MDA. The nongender-specific expression of CD36 underscores its potential importance in MDA pathogenesis.