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基于机器学习筛选影响骨关节炎发展的坏死性凋亡基因。

Screening necroptosis genes influencing osteoarthritis development based on machine learning.

作者信息

Wang Yan, Guo Xiangjun, Wang Bo, Zheng Jiaxuan, Li Ke, Zhang Zhijie, Zhang Yuzhuan, Huang Hui

机构信息

Department of Hand Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.

Department of Surgery Two, Chengmai People's Hospital, Chengmai, China.

出版信息

Sci Rep. 2025 Mar 15;15(1):9019. doi: 10.1038/s41598-025-92911-y.

DOI:10.1038/s41598-025-92911-y
PMID:40089565
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11910570/
Abstract

Machine learning can be applied to identify key genes associated with osteoarthritis (OA). This study aimed to explore the differential expression of necroptosis-related genes (NRGs) during the progression of OA, identify key gene modules strongly linked to the onset of OA, and assess the role of CASP1 and its correlation with immune cell infiltration in OA. Gene expression profile data were obtained for OA and normal tissues: GSE55235 (10 OA and 10 normal synovial tissues) and GSE46750 (12 OA and 12 normal synovial tissues). Differential expression analysis identified 44 NRGs. Weighted gene co-expression network analysis revealed that the turquoise module, including 2037 genes, showed a strong correlation with OA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that these genes were predominantly involved in regulating the JNK cascade, cellular response to oxidative stress, and Toll-like receptor signalling pathways. The support vector machine model exhibited the highest predictive performance (area under the curve of 0.883). Additionally, CASP1 expression in OA tissues was considerably elevated compared to normal tissues and was strongly associated with immune cell infiltration. These findings deepen our understanding of the pathophysiological foundation of OA and identify possible molecular targets for creating innovative OA therapies.

摘要

机器学习可用于识别与骨关节炎(OA)相关的关键基因。本研究旨在探讨坏死性凋亡相关基因(NRGs)在OA进展过程中的差异表达,识别与OA发病密切相关的关键基因模块,并评估半胱天冬酶1(CASP1)的作用及其与OA中免疫细胞浸润的相关性。获取了OA组织和正常组织的基因表达谱数据:GSE55235(10个OA滑膜组织和10个正常滑膜组织)和GSE46750(12个OA滑膜组织和12个正常滑膜组织)。差异表达分析确定了44个NRGs。加权基因共表达网络分析显示,包含2037个基因的绿松石模块与OA呈强相关。基因本体论和京都基因与基因组百科全书富集分析表明,这些基因主要参与调节JNK级联反应、细胞对氧化应激的反应以及Toll样受体信号通路。支持向量机模型表现出最高的预测性能(曲线下面积为0.883)。此外,与正常组织相比,OA组织中CASP1的表达显著升高,且与免疫细胞浸润密切相关。这些发现加深了我们对OA病理生理基础的理解,并确定了可能用于创新OA治疗的分子靶点。

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本文引用的文献

1
TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.源自骨骼干细胞的TNFAIP3通过抑制软骨下成骨细胞的坏死性凋亡减轻大鼠骨关节炎
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基于生物信息学分析和机器学习的骨关节炎相关衰老生物标志物和免疫浸润特征的鉴定。
Front Immunol. 2023 Jul 12;14:1168780. doi: 10.3389/fimmu.2023.1168780. eCollection 2023.
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Machine learning identifies ferroptosis-related genes as potential diagnostic biomarkers for osteoarthritis.机器学习确定铁死亡相关基因作为骨关节炎潜在的诊断生物标志物。
Front Endocrinol (Lausanne). 2023 Jun 12;14:1198763. doi: 10.3389/fendo.2023.1198763. eCollection 2023.
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Ther Adv Musculoskelet Dis. 2023 Mar 14;15:1759720X231158198. doi: 10.1177/1759720X231158198. eCollection 2023.
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Machine learning in knee osteoarthritis: A review.膝关节骨关节炎中的机器学习:综述
Osteoarthr Cartil Open. 2020 May 4;2(3):100069. doi: 10.1016/j.ocarto.2020.100069. eCollection 2020 Sep.
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Necroptosis in pathogenesis of osteoarthritis and its therapeutic implications.骨关节炎发病机制中的细胞坏死性凋亡及其治疗意义。
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Apr 25;51(2):261-265. doi: 10.3724/zdxbyxb-2021-0402.
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Identification of Biomarkers Associated with Diagnosis of Osteoarthritis Patients Based on Bioinformatics and Machine Learning.基于生物信息学和机器学习的骨关节炎患者诊断相关生物标志物的鉴定。
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