Department of Orthopaedic Surgery, The First People's Hospital of Wenling, Wenzhou Medical University Affiliated Wenling Hospital, Chuan'an Nan Road NO 333, Wenling, 317500, Zhejiang, China.
Biochem Genet. 2023 Oct;61(5):2056-2075. doi: 10.1007/s10528-023-10359-z. Epub 2023 Mar 16.
Osteoarthritis (OA) is a serious threat to human health. However, the etiology and pathogenesis of the disease are not fully understood. Most researchers believe that the degeneration and imbalance of articular cartilage, extracellular matrix, and subchondral bone are the fundamental causes of osteoarthritis. However, recent studies have shown that synovial lesions may precede cartilage, which may be an important precipitating factor in the early stage of OA and the whole course of the disease. This study aimed to conduct an analysis based on sequence data from the Gene Expression Omnibus (GEO) database to investigate the presence of effective biomarkers in the synovial tissue of osteoarthritis for the diagnosis and control of OA progression. In this study, the differentially expressed OA-related genes (DE-OARGs) in osteoarthritis synovial tissues were extracted in the GSE55235 and GSE55457 datasets using the Weighted Gene Co-expression Network Analysis (WGCNA) and limma. Least-Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to select the diagnostic genes based on the DE-OARGs by glmnet package. 7 genes were selected as diagnostic genes including SAT1, RLF, MAFF, SIK1, RORA, ZNF529, and EBF2. Subsequently, the diagnostic model was constructed and the results of the Area Under the Curve (AUC) demonstrated that the diagnostic model had high diagnostic performance for OA. Additionally, among the 22 immune cells of the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and the 24 immune cells of the single sample Gene Set Enrichment Analysis (ssGSEA), 3 immune cells and 5 immune cells were different between the OA and normal samples, respectively. The expression trends of the 7 diagnostic genes were consistent in the GEO datasets and the results of the real-time reverse transcription PCR (qRT-PCR). The results of this study demonstrate that these diagnostic markers have important significance in the diagnosis and treatment of OA, and will provide further evidence for the clinical and functional studies of OA.
骨关节炎(OA)是严重威胁人类健康的疾病之一。然而,其病因和发病机制尚未完全阐明。大多数研究人员认为关节软骨、细胞外基质和软骨下骨的退变和失衡是骨关节炎的根本原因。然而,最近的研究表明滑膜病变可能先于软骨,这可能是 OA 早期及疾病全过程中的一个重要诱发因素。本研究旨在基于基因表达综合数据库(GEO)中的序列数据进行分析,以探讨 OA 患者滑膜组织中是否存在有效的生物标志物,用于 OA 的诊断和控制疾病进展。在这项研究中,使用加权基因共表达网络分析(WGCNA)和 limma 在 GSE55235 和 GSE55457 数据集提取 OA 滑膜组织中差异表达的 OA 相关基因(DE-OARGs)。使用 glmnet 包基于 DE-OARGs 通过最小绝对收缩和选择算子(LASSO)算法选择诊断基因。筛选出 SAT1、RLF、MAFF、SIK1、RORA、ZNF529 和 EBF2 等 7 个基因作为诊断基因。随后构建诊断模型,AUC 结果表明该诊断模型对 OA 具有较高的诊断性能。此外,在 CIBERSORT 的 22 种免疫细胞和 ssGSEA 的 24 种免疫细胞中,OA 样本和正常样本之间分别有 3 种和 5 种免疫细胞存在差异。这 7 个诊断基因在 GEO 数据集和实时逆转录 PCR(qRT-PCR)中的表达趋势一致。本研究结果表明,这些诊断标志物在 OA 的诊断和治疗中具有重要意义,将为 OA 的临床和功能研究提供进一步证据。