Gene signature based on glycolysis is closely related to immune infiltration of patients with osteoarthritis

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2023-11-01 DOI:10.1016/j.cyto.2023.156377

Ziyi Chen, Yinghui Hua

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引用次数: 0

Abstract

Background

Osteoarthritis (OA) is a degenerative arthritis with high levels of clinical heterogeneity. Aberrant metabolism such as shifting from oxidative phosphorylation to glycolysis is a response to changes in the inflammatory microenvironment of OA. Therefore, there is a pressing need to identify novel glycolysis regulators during OA progression.

Methods

We systematically studied glycolysis patterns mediated by 141 glycolysis regulators in 74 human synovial samples and discussed the characteristics of the immune microenvironment modified by glycolysis. The random forest (RF) method was applied to screen candidate hub glycolysis regulators in OA. RT-qPCR was performed to validate these key regulators. Then distinct glycolysis patterns were identified, and systematic correlation between these glycolysis patterns and immune cell infiltration was analyzed. The glycolysis score was constructed to quantify glycolysis patterns together with immune infiltration of individual OA patient.

Results

56 glycolysis-related differentially expressed genes (DEGs) were identified between OA and non-OA samples. STC1, VEGFA, KDELR3, DDIT4 and PGAM1 were selected as candidate genes to predict the probability of OA. Two glycolysis patterns in OA were identified. Glycolysis cluster A with higher glycolysis score was related to an inflamed phenotype.

Conclusions

Taken together, our results established a glycolysis-based genetic signature for OA, guided in-depth studies on the metabolic mechanism of OA, and facilitated to explore new clinical treatment strategies.

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基于糖酵解的基因特征与骨关节炎患者的免疫浸润密切相关。

背景：骨关节炎（OA）是一种具有高度临床异质性的退行性关节炎。异常代谢，如从氧化磷酸化转变为糖酵解，是对OA炎症微环境变化的反应。因此，迫切需要在OA进展过程中鉴定新的糖酵解调节剂。方法：我们系统地研究了74个人类滑膜样品中141种糖酵解调节剂介导的糖酵解模式，并讨论了糖酵解修饰的免疫微环境的特征。应用随机森林（RF）方法筛选OA中枢糖酵解调节因子。进行RT-qPCR以验证这些关键调节因子。然后确定了不同的糖酵解模式，并分析了这些糖酵解方式与免疫细胞浸润之间的系统相关性。构建糖酵解评分以量化糖酵解模式以及OA患者个体的免疫浸润。结果：在OA和非OA样品中鉴定出56个糖酵解相关差异表达基因。选择STC1、VEGFA、KDELR3、DDIT4和PGAM1作为候选基因来预测OA的概率。OA中存在两种糖酵解模式。糖酵解评分较高的糖酵解簇A与炎症表型有关。结论：总之，我们的研究结果建立了基于糖酵解的OA遗传特征，指导了对OA代谢机制的深入研究，并有助于探索新的临床治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.