Elucidating the role of FBXW4 in osteoporosis: integrating bioinformatics and machine learning for advanced insight

Osteoporosis (OP), often termed the "silent epidemic," poses a substantial public health burden. Emerging insights into the molecular functions of FBXW4 have spurred interest in its potential roles across various diseases.

This study explored FBXW4 by integrating DEGs from GEO datasets GSE2208, GSE7158, GSE56815, and GSE35956 with immune-related gene compilations from the ImmPort repository. Gene selection was refined using advanced approaches, including LASSO regression and SVM-RFE. Functional enrichment of FBXW4-associated genes was assessed via GSEA and GSVA, identifying significant immune pathway involvement. Immune-related biological processes linked to FBXW4 expression were further evaluated using CIBERSORT and ESTIMATE algorithms. Validation of FBXW4 expression was performed using GSE35956.

A total of 13 hub genes were selected through LASSO and SVM-RFE analyses. Functional assays implicated FBXW4 in antiviral defense, cytokine production, and immune response modulation. Notably, FBXW4 expression correlated positively with several immune cell subsets, including memory B cells, activated memory CD4+ T cells, naive B cells, gamma delta T cells, M0 macrophages, follicular helper T cells, and naive CD4+ T cells, while showing a negative association with neutrophils.

This study uncovers a complex interplay between FBXW4 and immune processes in osteoporosis, suggesting its potential utility as a biomarker for OP diagnosis and monitoring. These findings lay the groundwork for future investigations into the therapeutic and diagnostic potential of FBXW4 in OP.