Identification of telomere-related diagnostic markers in osteoarthritis based on bioinformatics analysis and machine learning.

IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Sheng Xu, Jia Ye, Xiaochong Cai
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引用次数: 0

Abstract

Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues. Finally, potential drugs targeting candidate genes were predicted. Three telomere-related genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.

基于生物信息学分析和机器学习的骨关节炎端粒相关诊断标志物鉴定。
骨关节炎(OA)是最常见的关节疾病之一,衰老被认为是导致其进展的主要、不可逆转的因素。端粒相关的细胞衰老可能是影响OA过程的关键因素,但基于端粒相关基因的OA生物标志物尚未明确确定。数据集GSE51588、GSE12021和GSE55457从Gene Expression Omnibus数据库中检索。首先,利用R软件鉴定OA与正常样本之间的差异表达基因。随后,获得端粒相关差异表达基因(DETMRGs),并分析其功能富集。结合最小绝对收缩和选择算子、支持向量机递归特征消除和随机森林算法,从detmrg中选择OA诊断的特征基因。然后通过受试者工作特征(ROC)曲线和决策曲线分析验证这些特征基因的诊断价值。采用CIBERSORT和xCell评估OA组织中免疫细胞的浸润情况。最后,对候选基因靶向药物进行了预测。三个端粒相关基因PGD、SLC7A5和TKT已被确定为OA诊断的生物标志物,并通过ROC诊断试验得到证实。肥大细胞、中性粒细胞、普通淋巴样前体和与PGD、SLC7A5和TKT相关的嗜酸性粒细胞的免疫浸润减少。识别端粒相关基因PGD、SLC7A5和TKT作为OA的潜在诊断生物标志物具有重要意义,因为它为端粒相关基因在OA中的作用提供了有价值的见解。这一发现也为OA的诊断和治疗提供了有价值的信息。
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来源期刊
Korean Journal of Physiology & Pharmacology
Korean Journal of Physiology & Pharmacology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
CiteScore
3.20
自引率
5.00%
发文量
53
审稿时长
6-12 weeks
期刊介绍: The Korean Journal of Physiology & Pharmacology (Korean J. Physiol. Pharmacol., KJPP) is the official journal of both the Korean Physiological Society (KPS) and the Korean Society of Pharmacology (KSP). The journal launched in 1997 and is published bi-monthly in English. KJPP publishes original, peer-reviewed, scientific research-based articles that report successful advances in physiology and pharmacology. KJPP welcomes the submission of all original research articles in the field of physiology and pharmacology, especially the new and innovative findings. The scope of researches includes the action mechanism, pharmacological effect, utilization, and interaction of chemicals with biological system as well as the development of new drug targets. Theoretical articles that use computational models for further understanding of the physiological or pharmacological processes are also welcomed. Investigative translational research articles on human disease with an emphasis on physiology or pharmacology are also invited. KJPP does not publish work on the actions of crude biological extracts of either unknown chemical composition (e.g. unpurified and unvalidated) or unknown concentration. Reviews are normally commissioned, but consideration will be given to unsolicited contributions. All papers accepted for publication in KJPP will appear simultaneously in the printed Journal and online.
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