Zhang Yueqi, Yang Yi, Wang Chenzhong, Wan Shengcheng, Yao Zhenjun, Zhang Ying, Liu Jinyu, Zhang Chi
Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
DNA Cell Biol. 2020 Oct 16. doi: 10.1089/dna.2020.5552.
The pathogenesis of osteoarthritis (OA) is still unclear. It is therefore important to identify relevant diagnostic marker genes for OA. We performed an integrated analysis with multiple microarray data cohorts to identify potential transcriptome markers of OA development. Further, to identify OA diagnostic markers, we established gene regulatory networks based on the protein-protein interaction network involved in these differentially expressed genes (DEGs). Using support vector machine (SVM) pattern recognition, a diagnostic model for OA prediction and prevention was established. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 190 DEGs were mainly enriched in pathways like the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, mitogen-activated protein kinase signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, and osteoclast differentiation. Eight hub genes (, , , , , , , and ) were considered potential diagnostic biomarkers for OA, the area under curve (AUC) was >0.95, which showed high accuracy. The sensitivity and specificity of the SVM model of OA based on these eight genes reached 100% in multiple external verification cohorts. Our research provides a theoretical basis for OA diagnosis for clinicians.
骨关节炎(OA)的发病机制仍不清楚。因此,识别OA相关的诊断标志物基因很重要。我们对多个微阵列数据队列进行了综合分析,以识别OA发展的潜在转录组标志物。此外,为了识别OA诊断标志物,我们基于这些差异表达基因(DEG)所涉及的蛋白质-蛋白质相互作用网络建立了基因调控网络。使用支持向量机(SVM)模式识别,建立了OA预测和预防的诊断模型。京都基因与基因组百科全书通路分析显示,190个DEG主要富集于肿瘤坏死因子信号通路、白细胞介素-17信号通路、丝裂原活化蛋白激酶信号通路、活化B细胞核因子κ-轻链增强子信号通路和破骨细胞分化等通路。八个枢纽基因(,,,,,,和)被认为是OA的潜在诊断生物标志物,曲线下面积(AUC)>0.95,显示出高准确性。基于这八个基因的OA的SVM模型在多个外部验证队列中的敏感性和特异性达到100%。我们的研究为临床医生进行OA诊断提供了理论依据。