本研究旨在阐明牙周炎中铁死亡相关基因的生物学功能，以及它们与免疫浸润等肿瘤微环境（TME）特征的相关性。旨在为牙周炎的临床管理提供铁死亡的潜在诊断标志物。利用基因表达综合库（GEO）中的牙周炎相关微阵列数据集GSE16134和先前研究中确定的一组528个铁死亡相关基因，本研究揭示了差异表达牙周炎中铁死亡相关基因。随后，构建了蛋白质-蛋白质相互作用网络。探索了牙周炎的亚型，然后通过免疫细胞浸润和基因集富集分析进行验证。采用随机森林和 SVM（支持向量机）两种算法来揭示牙周炎潜在的铁死亡诊断标志物。进一步评估了这些标记物的诊断功效、免疫相关性和潜在的转录调控网络。最后，对牙周炎差异表达铁死亡标志物的潜在靶向药物进行了预测。从9个牙周炎样本与对照组的829个差异表达基因中，共鉴定出36个铁死亡相关基因（30个上调，6个下调）。随后的机器学习算法筛选突出了4个关键基因：SLC1A5(Solute Carrier Family 1 Member 5)、SLC2A14(Solute Carrier Family 1 Member 14)、LURAP1L(Leucine Rich Adapter Protein 1 Like)和HERPUD1(Homocysteine Inducible ER Protein With Ubiquitin Like)域1）。在时间相关 ROC 分析的支持下，对这 4 个关键基因的探索证明了可靠性，而免疫浸润结果表明关键基因与免疫因素之间存在很强的相关性。此外，对四个关键基因进行了基因集富集分析（GSEA），揭示了对牙周炎具有显着影响的 GO/KEGG 途径的富集。最后，该研究预测了牙周炎中与这些关键基因相关的潜在转录调控网络和靶向药物。本研究中鉴定的铁死亡相关基因，包括SLC1A5、SLC2A14、LURAP1L和HERPUD1，可能作为牙周炎的新诊断和治疗靶点。它们可能通过免疫浸润、细胞代谢和炎症趋化等机制参与牙周炎的发生和发展，可能将铁死亡途径与牙周炎的进展联系起来。氟洛酰胺、L-733060、美金刚、丁苯那嗪和 WAY-213613 等靶向药物有望对与这些铁死亡相关基因相关的牙周炎进行潜在的治疗干预。© 2024。作者。

This study aims to elucidate the biological functions of ferroptosis-related genes in periodontitis, along with their correlation to tumor microenvironment (TME) features such as immune infiltration. It aims to provide potential diagnostic markers of ferroptosis for clinical management of periodontitis.Utilizing the periodontitis-related microarray dataset GSE16134 from the Gene Expression Omnibus (GEO) and a set of 528 ferroptosis-related genes identified in prior studies, this research unveils differentially expressed ferroptosis-related genes in periodontitis. Subsequently, a protein-protein interaction network was constructed. Subtyping of periodontitis was explored, followed by validation through immune cell infiltration and gene set enrichment analyses. Two algorithms, randomForest and SVM(Support Vector Machine), were employed to reveal potential ferroptosis diagnostic markers for periodontitis. The diagnostic efficacy, immune correlation, and potential transcriptional regulatory networks of these markers were further assessed. Finally, potential targeted drugs for differentially expressed ferroptosis markers in periodontitis were predicted.A total of 36 ferroptosis-related genes (30 upregulated, 6 downregulated) were identified from 829 differentially expressed genes between 9 periodontitis samples and the control group. Subsequent machine learning algorithm screening highlighted 4 key genes: SLC1A5(Solute Carrier Family 1 Member 5), SLC2A14(Solute Carrier Family 1 Member 14), LURAP1L(Leucine Rich Adaptor Protein 1 Like), and HERPUD1(Homocysteine Inducible ER Protein With Ubiquitin Like Domain 1). Exploration of these 4 key genes, supported by time-correlated ROC analysis, demonstrated reliability, while immune infiltration results indicated a strong correlation between key genes and immune factors. Furthermore, Gene Set Enrichment Analysis (GSEA) was conducted for the four key genes, revealing enrichment in GO/KEGG pathways that have a significant impact on periodontitis. Finally, the study predicted potential transcriptional regulatory networks and targeted drugs associated with these key genes in periodontitis.The ferroptosis-related genes identified in this study, including SLC1A5, SLC2A14, LURAP1L, and HERPUD1, may serve as novel diagnostic and therapeutic targets for periodontitis. They are likely involved in the occurrence and development of periodontitis through mechanisms such as immune infiltration, cellular metabolism, and inflammatory chemotaxis, potentially linking the ferroptosis pathway to the progression of periodontitis. Targeted drugs such as flurofamide, L-733060, memantine, tetrabenazine, and WAY-213613 hold promise for potential therapeutic interventions in periodontitis associated with these ferroptosis-related genes.© 2024. The Author(s).