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阐明FBXW4在骨质疏松症中的作用:整合生物信息学和机器学习以获得深入见解。

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

作者信息

Li Jinxiao, Li Jing, Zheng Man, Liu Jinxing, Zhao Xinyou

机构信息

First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

Dongying Traditional Chinese Medicine Hospital, Dongying, Shandong, China.

出版信息

BMC Pharmacol Toxicol. 2025 Jan 29;26(1):20. doi: 10.1186/s40360-025-00844-z.

Abstract

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.

摘要

背景

骨质疏松症(OP)常被称为“无声的流行病”,给公共卫生带来了沉重负担。对FBXW4分子功能的新见解激发了人们对其在各种疾病中潜在作用的兴趣。

方法

本研究通过将来自GEO数据集GSE2208、GSE7158、GSE56815和GSE35956的差异表达基因(DEGs)与来自ImmPort数据库的免疫相关基因汇编进行整合,对FBXW4进行了探索。使用包括套索回归和支持向量机递归特征消除(SVM-RFE)在内的先进方法对基因进行筛选。通过基因集富集分析(GSEA)和基因集变异分析(GSVA)评估与FBXW4相关基因的功能富集情况,确定其显著参与的免疫途径。使用CIBERSORT和ESTIMATE算法进一步评估与FBXW4表达相关的免疫相关生物学过程。利用GSE35956对FBXW4的表达进行验证。

结果

通过套索回归和SVM-RFE分析共筛选出13个核心基因。功能分析表明FBXW4参与抗病毒防御、细胞因子产生和免疫反应调节。值得注意的是,FBXW4的表达与多个免疫细胞亚群呈正相关,包括记忆B细胞、活化的记忆CD4+T细胞、幼稚B细胞、γδT细胞、M0巨噬细胞、滤泡辅助性T细胞和幼稚CD4+T细胞,而与中性粒细胞呈负相关。

结论

本研究揭示了FBXW4与骨质疏松症免疫过程之间的复杂相互作用,表明其作为OP诊断和监测生物标志物的潜在用途。这些发现为未来研究FBXW4在OP中的治疗和诊断潜力奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/207d/11781060/1c7e2b8074e0/40360_2025_844_Fig1_HTML.jpg

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