Department of Periodontics, Panyu Branch, Stomatological Hospital, School of Stomatology, Southern Medical University, No.366 Jiangnan Dadao Nan, Haizhu District, Guangzhou, Guangdong, 510220, China.
Department of Histology and Embryology, Xiangya School of Medicine, Central South University, No. 172 Tongzipo Road, Yuelu District, Changsha, 410006, China.
BMC Oral Health. 2024 May 27;24(1):611. doi: 10.1186/s12903-024-04342-2.
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.
本研究旨在阐明与牙周炎相关的铁死亡相关基因的生物学功能，以及它们与肿瘤微环境（TME）特征（如免疫浸润）的相关性。它旨在为牙周炎的临床管理提供潜在的铁死亡诊断标志物。
利用基因表达综合数据库（GEO）中牙周炎相关的微阵列数据集 GSE16134 和之前研究中确定的 528 个铁死亡相关基因，本研究揭示了牙周炎中差异表达的铁死亡相关基因。随后，构建了蛋白质-蛋白质相互作用网络。对牙周炎进行了分型研究，并通过免疫细胞浸润和基因集富集分析进行了验证。使用随机森林和 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志物的诊断效能、免疫相关性和潜在的转录调控网络。最后，预测了牙周炎中差异表达的铁死亡标志物的潜在靶向药物。
从 9 个牙周炎样本与对照组之间的 829 个差异表达基因中鉴定出 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（溶质载体家族 1 成员 5）、SLC2A14（溶质载体家族 1 成员 14）、LURAP1L（亮氨酸丰富适配器蛋白 1 样）和 HERPUD1（同型半胱氨酸诱导 ER 蛋白具有泛素样结构域 1）。基于时间相关的 ROC 分析的这 4 个关键基因的探索表明其具有可靠性，而免疫浸润结果表明关键基因与免疫因子之间存在很强的相关性。此外，对这四个关键基因进行了基因集富集分析（GSEA），发现它们在与牙周炎相关的 GO/KEGG 途径中富集。最后，该研究预测了与这些关键基因在牙周炎相关的潜在转录调控网络和靶向药物。
本研究鉴定的铁死亡相关基因，包括 SLC1A5、SLC2A14、LURAP1L 和 HERPUD1，可能成为牙周炎的新型诊断和治疗靶点。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。氟罗氟酰胺、L-733060、美金刚、四苯嗪和 WAY-213613 等靶向药物可能为这些铁死亡相关基因相关的牙周炎的潜在治疗干预提供了希望。
