BMC pharmacology & toxicology · 2025
Elucidating the role of FBXW4 in osteoporosis: integrating bioinformatics and machine learning for advanced insight.
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Li Jinxiao, Li Jing, Zheng Man, Liu Jinxing, Zhao Xinyou
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.