ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1597219
This article is part of the Research TopicCommunity Series in Immunological Precision Therapeutics: Integrating Multi-Omics Technologies and Comprehensive Approaches for Personalized Immune Intervention: Volume IIView all 20 articles
Identification of immune-related diagnostic genes and immune cell infiltration in aseptic loosening of prostheses after total hip arthroplasty by integrated bioinformatics analysis and experimental confirmation
Provisionally accepted
Yunke Liu
Xiaming Liang
Shuo QiangYonghui Dong
Xin ZhaoLichao MaZhihua YanSongkai Yue
Yifan Huang*
Jia Zheng*- Department of Orthopedics, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou, China
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Background: Aseptic loosening (AL) of hip prostheses is one of the main reasons for revision total hip arthroplasty (rTHA). However, the transcriptomic characteristics of AL are scarcely understood. This study aimed to discover candidate biomarkers for the diagnosis of AL.The interface membrane from 4 patients with AL of hip prostheses and the synovium samples from 4 patients with periprosthetic femoral fracture after THA were analyzed via RNA sequencing. Integrated bioinformatics analysis was employed to identify immune-related hub genes in AL. Immune cell infiltration analysis and correlation analysis were performed.Connectivity Map analysis was utilized to predict the potential small molecule compounds for AL treatment. Western blotting and histological staining were used to verify the expression of hub genes in AL.Results: A total of 2184 DEGs in AL samples, including 2050 up-regulated genes and 134 down-regulated genes, DEGs were mainly enriched in immune cell-related signaling pathways and immune-related processes. Immune cell infiltration analysis showed that the proportion of M1 Macrophages increased in AL. Three genes closely related to M1 macrophages were screened, including CD68, CD163, and SPP1, according to the results of correlation analysis.Hematoxylin-eosin staining showed that the synovitis score of AL samples was significantly higher than controls (average 6.2 vs. 3.8). Western blotting and immunohistochemical analysis showed that the expression of CD68, CD163, and SPP1 in AL group was significantly higher than that in the control group. The top 10 compounds with the highest negative scores were predicted to be potential therapeutic drugs for the treatment of AL.Preliminary transcriptomic signatures suggested that CD68, CD163, and SPP1 may serve as potential biomarkers for AL, offering a novel research perspective for future diagnosis and therapeutic intervention of AL.
Keywords: Aseptic loosening, Total hip arthroplasty, Macrophages, bioinformatics, Immune infiltration
Received: 20 Mar 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Liu, Liang, Qiang, Dong, Zhao, Ma, Yan, Yue, Huang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yifan Huang, Department of Orthopedics, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou, China
Jia Zheng, Department of Orthopedics, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou, China
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