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整合生物信息学分析揭示了骨关节炎发病机制和诊断生物标志物的新见解。

Integrative bioinformatics analysis reveals novel insights into osteoarthritis pathogenesis and diagnostic biomarkers.

作者信息

Chen Qipeng, Li Xiaodong, Li Pengfei, Liu Hongpeng, Zhang Qi, He Linqin, Tang Zonghan, Song Hanbing

机构信息

Department of Orthopaedics and Traumatology III, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150040, China.

Department of Orthopaedics, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150040, China.

出版信息

BMC Musculoskelet Disord. 2024 Dec 5;25(1):999. doi: 10.1186/s12891-024-08124-3.

Abstract

BACKGROUND

Osteoarthritis (OA) is a prevalent joint disorder characterized by degeneration and inflammation. Understanding its molecular mechanisms is crucial for diagnosis and treatment.

METHODS

We employed bioinformatics analyses to study OA using gene expression data. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network analysis were conducted. Enrichment analyses were performed to elucidate the biological significance of identified genes. Additionally, signature genes were identified using LASSO regression analysis, and a diagnostic nomogram was developed. qRT-PCR was conducted to confirm the expression levels of signature genes.

RESULTS

We identified 200 differentially expressed genes (DEGs) and a lightgreen module strongly correlated with OA. Within this module, 97 core genes were identified. Fifteen core lipopolysaccharide-related genes (LRGs) were found, enriched in immune and inflammatory pathways. Three hub genes (CCL3, ZFP36, and CCN1) emerged as potential biomarkers for OA diagnosis, with a nomogram showing high predictive accuracy, and validated by using clinical samples. Gene set enrichment analysis (GSEA) revealed distinct signaling pathways associated with the signature genes. Immunological analysis indicated altered immune profiles in OA, with the signature genes influencing immune cell infiltration and immune response pathways.

CONCLUSION

Our study provides insights into OA pathogenesis and identifies potential diagnostic biomarkers. The developed nomogram shows promise for accurate OA diagnosis. Furthermore, the signature genes play crucial roles in modulating the immune microenvironment in OA, suggesting their therapeutic potential.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景

骨关节炎(OA)是一种以退变和炎症为特征的常见关节疾病。了解其分子机制对诊断和治疗至关重要。

方法

我们利用基因表达数据,采用生物信息学分析方法研究OA。进行了差异表达分析、加权基因共表达网络分析(WGCNA)和蛋白质-蛋白质相互作用(PPI)网络分析。进行富集分析以阐明已鉴定基因的生物学意义。此外,使用LASSO回归分析鉴定特征基因,并绘制诊断列线图。进行qRT-PCR以确认特征基因的表达水平。

结果

我们鉴定出200个差异表达基因(DEG)和一个与OA高度相关的浅绿模块。在该模块中,鉴定出97个核心基因。发现15个核心脂多糖相关基因(LRG),富集于免疫和炎症途径。三个枢纽基因(CCL3、ZFP36和CCN1)成为OA诊断的潜在生物标志物,列线图显示出高预测准确性,并通过临床样本进行了验证。基因集富集分析(GSEA)揭示了与特征基因相关的不同信号通路。免疫学分析表明OA中免疫谱发生改变,特征基因影响免疫细胞浸润和免疫反应途径。

结论

我们的研究为OA发病机制提供了见解,并鉴定出潜在的诊断生物标志物。所绘制的列线图在准确诊断OA方面显示出前景。此外,特征基因在调节OA免疫微环境中起关键作用,表明它们具有治疗潜力。

临床试验编号

不适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b11/11619307/dba329fcda99/12891_2024_8124_Fig1_HTML.jpg

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