Wu Zixuan, Long Xi, Tan Kang, Yao Xiaolei, Peng Qinghua
Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan Province, China.
Department of Ophthalmology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410007, Hunan Province, China.
Mediators Inflamm. 2025 Jun 13;2025:7061507. doi: 10.1155/mi/7061507. eCollection 2025.
Nonspecific orbital inflammation (NSOI) is a heterogeneous inflammatory disorder of the orbit with an unclear etiology. ATP2A3, a key regulator of calcium homeostasis in the endoplasmic reticulum (ER), may play a pivotal role in NSOI pathogenesis. Its potential as a diagnostic biomarker merits thorough investigation. Differentially expressed genes (DEGs) common to two GEO datasets (GSE58331 and GSE105149) were intersected with immune-related genes from the ImmPort database, yielding 89 candidates. ATP2A3 was prioritized using machine learning (ML) approaches, including LASSO, support vector machine (SVM)-RFE, and weighted gene coexpression network analysis (WGCNA). Functional enrichment was assessed using GSEA and GSVA based on genes co-expressed with ATP2A3. Immune microenvironment characteristics were evaluated using CIBERSORT and ESTIMATE. Expression of ATP2A3 was validated in GSE105149. Fifteen hub genes were identified, with ATP2A3 strongly linked to immune-related pathways. Genes positively correlated with ATP2A3 were enriched in sensory perception and extracellular matrix (ECM) organization. Immune infiltration analysis revealed a positive association between ATP2A3 expression and memory B cells, M2 macrophages, resting mast cells, monocytes, and regulatory T cells (Tregs), while naive B cells and plasma cells were negatively associated. ATP2A3 exhibited significant diagnostic potential for distinguishing NSOI. In the context of NSOI, we identify ATP2A3 as a novel contributor to immune-driven pathogenesis. Its significant dysregulation in NSOI tissues relative to healthy controls underscores its potential as a prognostic marker within the inflammatory microenvironment.
非特异性眼眶炎症（NSOI）是一种病因不明的眼眶异质性炎症性疾病。ATP2A3是内质网（ER）中钙稳态的关键调节因子，可能在NSOI发病机制中起关键作用。其作为诊断生物标志物的潜力值得深入研究。将两个GEO数据集（GSE58331和GSE105149）中的差异表达基因（DEG）与ImmPort数据库中的免疫相关基因进行交叉分析，得到89个候选基因。使用机器学习（ML）方法对ATP2A3进行优先级排序，包括套索回归、支持向量机（SVM）-递归特征消除和加权基因共表达网络分析（WGCNA）。基于与ATP2A3共表达的基因，使用基因集富集分析（GSEA）和基因集变异分析（GSVA）评估功能富集情况。使用CIBERSORT和ESTIMATE评估免疫微环境特征。在GSE105149中验证了ATP2A3的表达。鉴定出15个枢纽基因，其中ATP2A3与免疫相关途径密切相关。与ATP2A3呈正相关的基因在感觉感知和细胞外基质（ECM）组织中富集。免疫浸润分析显示，ATP2A3表达与记忆B细胞、M2巨噬细胞、静息肥大细胞、单核细胞和调节性T细胞（Tregs）呈正相关，而与幼稚B细胞和浆细胞呈负相关。ATP2A3在区分NSOI方面具有显著的诊断潜力。在NSOI的背景下，我们将ATP2A3确定为免疫驱动发病机制的一个新因素。与健康对照相比，其在NSOI组织中的显著失调突出了其在炎症微环境中作为预后标志物的潜力。
