Huashan Hospital, Fudan University, Shanghai 200040, China.
Biomolecules. 2023 Mar 16;13(3):539. doi: 10.3390/biom13030539.
With the increasingly serious burden of osteoarthritis (OA) on modern society, it is urgent to propose novel diagnostic biomarkers and differentiation models for OA. 7-methylguanosine (mG), as one of the most common base modification forms in post transcriptional regulation, through which the seventh position N of guanine (G) of messenger RNA is modified by methyl under the action of methyltransferase; it has been found that it plays a crucial role in different diseases. Therefore, we explored the relationship between OA and mG. Based on the expression level of 18 mG-related regulators, we identified nine significant regulators. Then, via a series of methods of machine learning, such as support vector machine recursive feature elimination, random forest and lasso-cox regression analysis, a total of four significant regulators were further identified (DCP2, EIF4E2, LARP1 and SNUPN). Additionally, according to the expression level of the above four regulators, two different mG-related clusters were divided via consensus cluster analysis. Furthermore, via immune infiltration, differential expression analysis and enrichment analysis, we explored the characteristic of the above two different clusters. An mG-related scoring model was constructed via the PCA algorithm. Meanwhile, there was a different immune status and correlation for immune checkpoint inhibitors between the above two clusters. The expression difference of the above four regulators was verified via real-time quantitative polymerase chain reaction. Overall, a total of four biomarkers were identified and two different mG-related subsets of OA with different immune microenvironment were obtained. Meanwhile, the construction of mG-related Scoring model may provide some new strategies and insights for the therapy and diagnosis of OA patients.
随着骨关节炎（OA）在现代社会负担的日益加重，迫切需要提出新的 OA 诊断生物标志物和鉴别模型。7-甲基鸟苷（mG）作为最常见的转录后调控碱基修饰形式之一，通过该形式，信使 RNA 上的第七位 N （G）在甲基转移酶的作用下被甲基修饰；现已发现其在不同疾病中发挥关键作用。因此，我们探讨了 OA 与 mG 的关系。基于 18 个 mG 相关调节因子的表达水平，我们鉴定出 9 个重要的调节因子。然后，通过一系列机器学习方法，如支持向量机递归特征消除、随机森林和lasso-cox 回归分析，进一步鉴定出 4 个重要的调节因子（DCP2、EIF4E2、LARP1 和 SNUPN）。此外，根据上述 4 个调节因子的表达水平，通过共识聚类分析，将其分为 2 个不同的 mG 相关聚类。进一步通过免疫浸润、差异表达分析和富集分析，探索上述两个不同聚类的特征。通过 PCA 算法构建 mG 相关评分模型。同时，上述两个聚类之间存在不同的免疫状态和免疫检查点抑制剂相关性。通过实时定量聚合酶链反应验证了上述 4 个调节因子的表达差异。总体而言，鉴定出了 4 个生物标志物，获得了具有不同免疫微环境的 OA 两个不同的 mG 相关亚群。同时，mG 相关评分模型的构建可能为 OA 患者的治疗和诊断提供一些新的策略和思路。
