Suzhou Medical College of Soochow University, Soochow, 215000, China; Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200050, China.
Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200050, China.
Arch Biochem Biophys. 2023 Sep 1;745:109713. doi: 10.1016/j.abb.2023.109713. Epub 2023 Aug 4.
Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.
桥本甲状腺炎（HT）是一种自身免疫性疾病，其免疫紊乱与氧化应激（OS）之间存在复杂的相互作用。本研究旨在通过整合生物信息学分析和临床验证，发现与 HT 免疫和 OS 失调相关的生物标志物和潜在治疗靶点。对 GEO 数据库中的 GSE138198 数据集进行差异基因表达分析，鉴定出 HT 中的 1490 个差异表达基因（DEGs），其中包括 883 个上调基因和 607 个下调基因。加权基因共表达网络分析探讨了与 HT 相关的模块基因。将差异表达模块基因与免疫相关和 OS 相关基因重叠，鉴定出 HT 中与免疫和 OS 相关的 8 个差异表达模块基因（DEIOGs）。蛋白质-蛋白质相互作用网络分析鉴定出五个枢纽基因（TNFAIP3、FOS、PTK2B、STAT1 和 MMP9）。我们在 GSE29315 数据集和临床甲状腺样本中验证了四个枢纽基因（TNFAIP3、PTK2B、STAT1 和 MMP9），它们对 HT 具有较高的诊断准确性（AUC＞0.7）。这四个基因在临床甲状腺样本中的表达与血清甲状腺过氧化物酶抗体、甲状腺球蛋白抗体水平和炎症浸润评分呈正相关。免疫谱分析显示 HT 存在独特的表型，如 B 细胞记忆、单核细胞和巨噬细胞。此外，所有枢纽基因与单核细胞呈负相关。进一步进行了 miRNA-mRNA 网络分析，建立了包含四个枢纽基因、238 个 miRNA 和 32 个 TFs 的调控网络。这些结果表明，免疫细胞在 HT 的发生发展中起着关键作用，枢纽基因 TNFAIP3、PTK2B、STAT1 和 MMP9 可能通过免疫和 OS 相关信号通路成为 HT 的关键参与者。我们的研究结果可能为 HT 的发病机制和治疗监测提供有价值的见解。
