Machine learning identifies ferroptosis-related genes as potential diagnostic biomarkers for osteoarthritis

Frontiers in Endocrinology

Endocrinology

Junpu Huang¹  Jun Yao¹  Meimei Xiao¹  Yue Qiu¹  Zhenpei Wen¹  Lin Li¹  Jinzhi Meng¹  Xing Huang¹  Yang Cai¹  Miaomiao Zhu²  Xingqing Long²  Siyuan Chen²  Jingqi Li² 

[1] Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;First Clinical Medical College, Guangxi Medical University, Nanning, China;

关键词: osteoarthritis;    ferroptosis;    immune infiltration;    targeted therapy;    machine learning;   

DOI  :  10.3389/fendo.2023.1198763

 received in 2023-04-02, accepted in 2023-05-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundOsteoarthritis (OA) is one of the most common forms of degenerative arthritis and a major cause of pain and disability. Ferroptosis, a novel mode of cell death, has been verified to participate in the development of OA, but its mechanism is still unclear. This paper analyzed the ferroptosis-related genes (FRGs) in OA and explored their potential clinical value.MethodsWe downloaded data through the GEO database and screened for DEGs. Subsequently, FRGs were obtained using two machine learning methods, LASSO regression and SVM-RFE. The accuracy of the FRGs as disease diagnosis was identified using ROC curves and externally validated. The CIBERSORT analyzed the immune microenvironment rug regulatory network constructed through the DGIdb. The competitive endogenous RNA (ceRNA) visualization network was constructed to search for possible therapeutic targets. The expression levels of FRGs were verified by qRT-PCR and immunohistochemistry.ResultsIn this study, we found 4 FRGs. The ROC curve showed that the combined 4 FRGs had the highest diagnostic value. Functional enrichment analysis showed that the 4 FRGs in OA could influence the development of OA through biological oxidative stress, immune response, and other processes. qRT-PCR and immunohistochemistry verified the expression of these key genes, further confirming our findings. Monocytes and macrophages are heavily infiltrated in OA tissues, and the persistent state of immune activation may promote the progression of OA. ETHINYL ESTRADIOL was a possible targeted therapeutic agent for OA. Meanwhile, ceRNA network analysis identified some lncRNAs that could regulate the FRGs.ConclusionWe identify 4 FRGs (AQP8, BRD7, IFNA4, and ARHGEF26-AS1) closely associated with bio-oxidative stress and immune response, which may become early diagnostic and therapeutic targets for OA.

【 授权许可】

Unknown   
Copyright © 2023 Qiu, Yao, Li, Xiao, Meng, Huang, Cai, Wen, Huang, Zhu, Chen, Long and Li