ZhaYang Xiao-Zhi, Chen Yan-Xiong, Hua Wen-Da, Bai Zheng-Lin, Jin Yun-Peng, Zhao Xing-Wen, Liu Quan-Fu, Meng Zeng-Dong
Faculty of Medical Science, Kunming University of Science and Technology, Kunming, Yunnan, China.
Department of Orthopedic Surgery, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
BMC Musculoskelet Disord. 2025 May 26;26(1):517. doi: 10.1186/s12891-025-08779-6.
Branched-chain amino acids (BCAA) metabolism is significantly associated with osteoarthritis (OA), but the specific mechanism of BCAA related genes (BCAA-RGs) in OA is still unclear. Therefore, this research intended to identify potential biomarkers and mechanisms of action of BCAA-RGs in OA tissues.
Differential genes were obtained from the Gene Expression Omnibus (GEO) database and intersections were taken with BCAA-RGs to identify candidate genes. The underlying mechanisms were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, by combining three machine learning algorithms to identify genes with highly correlated OA features. In addition, created diagnostic maps and subject Receiver operating characteristic curves (ROCs) to assess the ability of the signature genes to diagnose OA and to predict their possible roles in molecular regulatory network axes and molecular signaling pathways.
Eight candidate genes were acquired by intersecting 4,178 DEGs and 14 BCAA-RGs. Subsequently, five candidate biomarkers were obtained, namely SLC3A2, SLC7A5, SLC43A2, SLC43A1, and SLC7A7. Importantly, SLC3A2 and SLC7A5 were validated by validation set and qRT-PCR. Furthermore, the nomogram constructed by SLC3A2 and SLC7A5 exhibited excellent accuracy in predicting the incidence of OA. The enrichment results demonstrated that SLC3A2 and SLC7A5 were significantly enriched in ribosome, insulin signaling pathway, olfactory transduction, etc. Meanwhile, we also found XIST regulated SLC7A5 through hsa-miR-30e-5p, and regulated SLC3A2 through hsa-miR-7-5p.OIP5-AS1 regulated SLC7A5 and SLC3A2 through hsa-miR-7-5p. By the way, 150 drugs were identified, including Acetaminophen and Acrylamide, which exhibited simultaneous targeting of these two biomarkers.
Based on bioinformatics, SLC3A2 and SLC7A5 were identified as biomarkers related to BCAA in OA, which may provide a new reference for the treatment and diagnosis of OA patients.
支链氨基酸（BCAA）代谢与骨关节炎（OA）显著相关，但BCAA相关基因（BCAA-RGs）在OA中的具体机制仍不清楚。因此，本研究旨在确定OA组织中BCAA-RGs的潜在生物标志物和作用机制。
从基因表达综合数据库（GEO）中获取差异基因，并与BCAA-RGs进行交集分析以确定候选基因。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）揭示潜在机制。随后，结合三种机器学习算法来识别与OA特征高度相关的基因。此外，创建诊断图和受试者操作特征曲线（ROC），以评估特征基因诊断OA的能力，并预测它们在分子调控网络轴和分子信号通路中的可能作用。
通过将4178个差异表达基因（DEGs）与14个BCAA-RGs进行交集分析，获得了8个候选基因。随后，获得了5个候选生物标志物，即溶质载体家族3成员2（SLC3A2）、溶质载体家族7成员5（SLC7A5）、溶质载体家族43成员2（SLC43A2）、溶质载体家族43成员1（SLC43A1）和溶质载体家族7成员7（SLC7A7）。重要的是，SLC3A2和SLC7A5在验证集和qRT-PCR中得到了验证。此外，由SLC3A2和SLC7A5构建的列线图在预测OA发病率方面表现出优异的准确性。富集结果表明，SLC3A2和SLC7A5在核糖体、胰岛素信号通路、嗅觉转导等方面显著富集。同时，我们还发现XIST通过hsa-miR-30e-5p调控SLC7A5，并通过hsa-miR-7-5p调控SLC3A2。OIP5-AS1通过hsa-miR-7-5p调控SLC7A5和SLC3A2。顺便说一下，鉴定出了150种药物，包括对乙酰氨基酚和丙烯酰胺，它们同时靶向这两种生物标志物。
基于生物信息学，SLC3A2和SLC7A5被鉴定为OA中与BCAA相关的生物标志物，这可能为OA患者的治疗和诊断提供新的参考。
