Integrative RNA‑seq analysis reveals immune‑related hub genes NR۴A۱ and FOSB in recurrent spontaneous abortion: A bioinformatics study

Background: Recurrent spontaneous abortion (RSA) impacts ۱-۵% of women of reproductive age, constituting a significant health issue. Despite advances in our understanding of RSA, the fundamental molecular mechanisms remain inadequately defined. Examining differentially expressed genes (DEGs) in RSA may yield essential insights into the disease’s pathophysiology and enable the identification of novel ameliorative targets. Objective: This study aimed to identify key DEGs, elucidate their interaction networks, and uncover potential hub regulators across decidua and villus tissues in RSA vs. control samples. Materials and Methods: In this bioinformatics study, we analyzed RNA‑seq datasets GSE۱۱۳۷۹۰ (decidua) and GSE۱۲۱۹۵۰ (villus) from the gene expression omnibus database using illumina‑aligned count matrices. Rigorous batch correction was performed using surrogate variable analysis, followed by differential expression analysis in DESeq۲ with thresholds of |log₂FC| ≥  ۲ and false discovery rate  <  ۰.۰۵. A high‑confidence protein-protein interaction network was constructed via STRING (confidence > ۰.۷), and functional enrichment analysis was conducted. Hub genes were identified using the maximal clique centrality, density of maximum neighborhood component, and maximum neighborhood component algorithms in CytoHubba, and the expression of top candidates was visualized across merged datasets. Results: After correction and integration, ۱۱۴ protein‑coding DEGs (۳۰ upregulated and ۸۴ downregulated) were identified. The protein-protein interaction network (۱۰۱ nodes, ۱۱۶ edges) was significantly enriched over random expectation (p  <  ۱×۱۰⁻¹⁶). Enrichment analysis highlighted immune‑related processes, including neutrophil chemotaxis and cytokine-mediated signaling. Cross‑algorithm analysis revealed NR۴A۱ and FOSB as consensus hubs, both significantly downregulated in RSA (NR۴A۱: log₂FC =  -۲.۱۵, p_adj  =  ۴.۷۸×۱۰⁻²⁰; FOSB: log₂FC  =  -۲.۹۶, p_adj  =  ۲.۴۶×۱۰⁻⁴⁰). Conclusion: Our integrative approach delineates immune-centric molecular dysfunction in RSA and highlights NR۴A۱ and FOSB as central regulatory genes that may drive disease pathogenesis. These findings pave the way for experimental validation and functional studies targeting immune-trophoblast signaling to inform diagnostic and therapeutic strategies in RSA.

کلیدواژه ها:

Spontaneous abortion ، Gene expression profiling ، Protein interaction mapping ، FOSB ، NR۴A۱. ، سقط خودبه خودی ، پروفایل بیان ژن ، نقشه برداری تعامل پروتئین ، FOSB ، NR۴A۱.