Yang Pusheng, Zhu Yiping, Miao Yaxin, Wang Tao, Liu Wenwen, Zhang Jiaxin, Ge Beilei, Sun Jing
Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Int J Med Sci. 2025 Jan 1;22(1):27-43. doi: 10.7150/ijms.101754. eCollection 2025.
Growing research suggests that endometriosis and systemic lupus erythematosus (SLE) are both chronic inflammatory diseases and closely related, but no studies have explored their common molecular characteristics and underlying mechanisms. Based on GEO datasets, differentially expressed genes in the endometriosis cohort and the SLE cohort were screened using Limma and weighted gene co-expression network analysis (WGCNA), and prediction signatures were constructed using LASSO logistic regression analysis, respectively. Four co-diagnostic genes (PMP22, QSOX1, REV3L, SP110) were identified for endometriosis and SLE. The nomogram, calibration curve, decision curve analyses (DCA), area under the receiver operating characteristic (AUC) curve and external datasets were used to evaluate the diagnostic and predictive value of co-diagnostic genes. The AUC value of the four co-diagnostic genes were higher than 0.85 in both endometriosis and SLE cohorts. Besides, functional enrichment analysis showed that DNA replication, base excision repair, cell cycle and cell adhesion molecules were significantly enriched. Multifactor regulatory network of four co-diagnostic genes was constructed including 96 TFs, 42 miRNA, 43 lncRNA, and 189 drugs, and Tributyrin was found to act on four co-diagnostic genes simultaneously. We identified and validated four co-diagnostic genes and revealed the potential molecular mechanisms of endometriosis and SLE, which is helpful for early diagnosis and targeted therapy. Our study provides a novel perspective for individualized treatment of patients with endometriosis and SLE.
越来越多的研究表明，子宫内膜异位症和系统性红斑狼疮（SLE）都是慢性炎症性疾病且密切相关，但尚无研究探讨它们的共同分子特征和潜在机制。基于基因表达综合数据库（GEO）数据集，分别使用Limma和加权基因共表达网络分析（WGCNA）筛选子宫内膜异位症队列和SLE队列中的差异表达基因，并使用套索逻辑回归分析构建预测特征。确定了四个用于子宫内膜异位症和SLE的联合诊断基因（外周髓鞘蛋白22、醌氧化还原酶1、DNA聚合酶ζ催化亚基、Sp110核小体相关蛋白）。使用列线图、校准曲线、决策曲线分析（DCA）、受试者操作特征（AUC）曲线下面积和外部数据集来评估联合诊断基因的诊断和预测价值。在子宫内膜异位症和SLE队列中，四个联合诊断基因的AUC值均高于0.85。此外，功能富集分析表明DNA复制、碱基切除修复、细胞周期和细胞粘附分子显著富集。构建了四个联合诊断基因的多因素调控网络，包括96个转录因子、42个微小RNA、43个长链非编码RNA和189种药物，并发现三丁酸甘油酯可同时作用于四个联合诊断基因。我们鉴定并验证了四个联合诊断基因，揭示了子宫内膜异位症和SLE的潜在分子机制，这有助于早期诊断和靶向治疗。我们的研究为子宫内膜异位症和SLE患者的个体化治疗提供了新的视角。
