Zhao Mingjian, Zhang Yetong, Zhao Hongliang
Graduate School, Dalian Medical University, Dalian, China.
Department of Burns and Plastic Surgery, Miyun Hospital, Capital Medical University, Beijing, China.
Front Surg. 2023 Jan 9;9:1060036. doi: 10.3389/fsurg.2022.1060036. eCollection 2022.
Burns are a common trauma associated with considerable mortality and morbidity. Although a lot is known regarding burns' pathogenesis, the involvement of ferroptosis is uncertain. Here, we aimed to explore vital ferroptosis-related genes and molecules in burns, through bioinformatics analysis, to uncover new effective therapeutic targets.
The FerrDb database was used to acquire ferroptosis-related genes and GSE19743 was downloaded from Gene Expression Omnibus (GEO), a dataset with analysis of control and burned individuals. Hub genes were selected with Cytoscape software, and Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Cox proportional hazard function and Kaplan-Meier survival analyses were implemented to screen prognosis-related genes. Additionally, the miRWalk database was used to acquire the miRNAs relevant to our hub genes function and analyzed for enrichment.
We identified 64 differentially expressed genes and through the intersection with ferroptosis-related genes, 10 were selected as hub genes. GO analysis revealed that the hub genes' most enriched activities were response to oxidative stress, pyridine-containing compound metabolic processes, and reactive oxygen species metabolic processes. KEGG pathways' analysis showed that these overlapped genes were enriched in several pathways, namely, in VEGF signaling. Furthermore, the molecular miRNA functions significantly enriched were signal transduction and cell communication, namely, the biological pathways of the glypican pathway and the ErbB receptor signaling network. SLC40A1 and GPT2 genes were found to be associated with overall survival, suggesting an important role in burn prognosis.
This study may improve our understanding of the underlying burn mechanisms and provide a new direction for the prevention of poor outcomes, advances in burns treatment, and drug development.
烧伤是一种常见的创伤，常伴有相当高的死亡率和发病率。尽管关于烧伤的发病机制已有很多了解，但铁死亡的参与情况尚不确定。在此，我们旨在通过生物信息学分析探索烧伤中与铁死亡相关的关键基因和分子，以发现新的有效治疗靶点。
使用FerrDb数据库获取与铁死亡相关的基因，并从基因表达综合数据库（GEO）下载GSE19743数据集，该数据集对对照个体和烧伤个体进行了分析。使用Cytoscape软件选择枢纽基因，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。实施Cox比例风险函数和Kaplan-Meier生存分析以筛选与预后相关的基因。此外，使用miRWalk数据库获取与我们的枢纽基因功能相关的miRNA并进行富集分析。
我们鉴定出64个差异表达基因，通过与铁死亡相关基因的交集，选择了10个作为枢纽基因。GO分析显示，枢纽基因最富集的活动是对氧化应激的反应、含吡啶化合物代谢过程和活性氧代谢过程。KEGG通路分析表明，这些重叠基因在多个通路中富集，即VEGF信号通路。此外，显著富集的分子miRNA功能是信号转导和细胞通讯，即磷脂酰肌醇蛋白聚糖途径和表皮生长因子受体（ErbB）信号网络的生物学途径。发现溶质载体家族40成员1（SLC40A1）和谷丙转氨酶2（GPT2）基因与总生存期相关，表明它们在烧伤预后中起重要作用。
本研究可能会增进我们对烧伤潜在机制的理解，并为预防不良结局、烧伤治疗进展和药物开发提供新的方向。
