Medical College, Guangxi University, Nanning 530000, China.
School of Information and Management, Guangxi Medical University, Nanning 530000, China.
Genes (Basel). 2022 Aug 23;13(9):1501. doi: 10.3390/genes13091501.
Osteoarthritis (OA) is a common chronic degenerative arthritis. Its treatment options are very limited. At present, hypoxia is a prominent factor in OA. This study aimed to re-explore the mechanism between hypoxia and OA, which provides new insights into the diagnosis and therapy of OA. We acquired the OA-related expression profiles of GSE48556, GSE55235, and GSE55457 for our analysis. Using gene set variation analysis (GSVA), we found significant differences in hypoxia. These differences result from multiple pathways, such as the p53 signaling pathway, cell senescence, the NF-kappa B signaling pathway, Ubiquitin-mediated proteolysis, and apoptosis. Meanwhile, the single-sample gene set enrichment analysis (ssGSEA) showed that hypoxia was significantly associated with the level of immune cell infiltration in the immune microenvironment. Thus, we believe that hypoxia is useful for the diagnosis and treatment of OA. We successfully constructed a novel hypoxia-related index (HRI) based on seven hypoxia-related genes (ADM, CDKN3, ENO1, NDRG1, PGAM1, SLC2A1, VEGFA) by least absolute shrinkage and binary logistic regression of the generalized linear regression. HRI showed potential for improving OA diagnosis through receiver operation characteristic (ROC) analysis (AUC training cohort = 0.919, AUC testing cohort = 0.985). Moreover, we found that celastrol, droxinostat, torin-2, and narciclasine may be potential therapeutic compounds for OA based on the Connectivity Map (CMap). In conclusion, hypoxia is involved in the development and progression of OA. HRI can improve diagnosis and show great potential in clinical application. Celastrol, droxinostat, torin-2, and narciclasine may be potential compounds for the treatment of OA patients.
骨关节炎（OA）是一种常见的慢性退行性关节炎。其治疗选择非常有限。目前，缺氧是 OA 的一个突出因素。本研究旨在重新探讨缺氧与 OA 之间的机制，为 OA 的诊断和治疗提供新的见解。我们获取了 GSE48556、GSE55235 和 GSE55457 中与 OA 相关的表达谱进行分析。使用基因集变异分析（GSVA），我们发现缺氧存在显著差异。这些差异是由多个途径引起的，如 p53 信号通路、细胞衰老、NF-kappa B 信号通路、泛素介导的蛋白水解和细胞凋亡。同时，单样本基因集富集分析（ssGSEA）显示，缺氧与免疫微环境中免疫细胞浸润水平显著相关。因此，我们认为缺氧对 OA 的诊断和治疗具有重要意义。我们成功构建了一种基于 7 个与缺氧相关基因（ADM、CDKN3、ENO1、NDRG1、PGAM1、SLC2A1、VEGFA）的最小绝对收缩和二进制逻辑回归的广义线性回归的新型缺氧相关指数（HRI）。通过接收者操作特征（ROC）分析（训练队列 AUC=0.919，测试队列 AUC=0.985），HRI 显示出改善 OA 诊断的潜力。此外，我们还发现，基于连接图谱（CMap）， celastrol、droxinostat、torin-2 和 narciclasine 可能是 OA 的潜在治疗化合物。总之，缺氧参与 OA 的发生和发展。HRI 可以提高诊断的准确性，并在临床应用中具有很大的潜力。Celastrol、droxinostat、torin-2 和 narciclasine 可能是 OA 患者潜在的治疗化合物。
