鉴定骨关节炎中与色氨酸代谢有关的生物标记物

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry and Biophysics Reports Pub Date : 2024-06-30 DOI:10.1016/j.bbrep.2024.101763
Junjun Yang , Ping Zhou , Tangbing Xu , Kaida Bo , Chenxin Zhu , Xu Wang , Jun Chang
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引用次数: 0

摘要

背景OA(骨关节炎)是一种常见的关节疾病,以关节软骨损伤为特征,影响整个关节组织,主要表现为关节疼痛、僵硬和活动受限。据报道,OA的发生和发展与色氨酸代谢的变化有关。因此,研究色氨酸代谢和OA相关基因有望找到治疗OA的新靶点。方法通过差异表达分析(OA样本与正常样本)获得GSE55235中的差异表达基因(DEGs)。通过色氨酸代谢相关基因(TMRGs)和 DEGs 的重叠获得色氨酸代谢相关 DEGs(TMR-DEGs)。然后,通过最小绝对收缩和选择算子(LASSO)、天真贝叶斯(NB)和支持向量机-递归特征消除(SVM-RFE)算法筛选生物标志物,建立诊断模型。随后,利用多种软件和数据库,根据诊断生物标志物进行基因组富集分析(Gene Set Enrichment Analysis,GSEA)和药物预测。结果在 OA 中发现了三个色氨酸代谢相关的生物标记物(TDO2、AOX1 和 SLC3A2)。GSEA分析表明,生物标志物与 "FoxO信号通路"、"剪接体 "和 "核糖体 "的功能有关。有七种药物对TDO2和AOX1具有治疗潜力。最终,与正常组相比,OA 组中 AOX1 和 SLC3A2 的表达显著降低。
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Identification of biomarkers related to tryptophan metabolism in osteoarthritis

Background

OA (osteoarthritis) is a common joint disease characterized by damage to the articular cartilage and affects the entire joint tissue, with its main manifestations being joint pain, stiffness, and limited movement.Currently,we know that OA is a complex process composed of inflammatory and metabolic factors.It is reported that the occurrence and development of OA is related to the change of tryptophan metabolism.Therefore, the study of tryptophan metabolism and OA related genes is hopeful to find a new therapeutic target for OA.

Methods

Differentially expressed genes (DEGs) in GSE55235 were gained via differential expression analysis (OA samples vs normal samples). The tryptophan metabolic related DEGs (TMR-DEGs) were obtained by overlapping tryptophan metabolism related genes (TMRGs) and DEGs. Further, biomarkers were screening via Least absolute shrinkage and selection operator (LASSO), naive bayes (NB) and supportvector machine-recursive feature elimination (SVM-RFE) algorithm to establish a diagnostic model. Afterward, Gene Set Enrichment Analysis (GSEA) and drug prediction were performed based on diagnostic biomarkers by multiple software and databases. Eventually, expression level of biomarker public databases was verified using real-time quantitative polymerase chain reaction (RT-qPCR).

Results

Three tryptophan metabolism related biomarkers (TDO2, AOX1 and SLC3A2) were identified in OA. GSEA analysis demonstrated that biomarkers were associated with the function of ‘FoxO signaling pathway’, ‘spliceosome’ and ‘ribosome’. There were seven drugs with therapeutic potential on TDO2 and AOX1. Ultimately, compared with normal group, expression of AOX1 and SLC3A2 in OA group remarkable lower.

Conclusion

Overall, three tryptophan metabolic related diagnostic biomarkers that associated with OA were obtained, which provided a original direction for the diagnosis and treatment of OA.

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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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