Abstract：
OBJECTIVE: The objective of this study was to discern ferroptosis-related genes (FRGs) linked to non-obstructive azoospermia and investigate the associated molecular mechanisms.
METHODS: A dataset related to azoospermia was retrieved from the Gene Expression Omnibus database, and FRGs were sourced from GeneCards. Ferroptosis-related differentially expressed genes (FRDEGs) were discerned. Subsequently, these genes underwent analyses encompassing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, as well as protein-protein interaction (PPI) networks and assessments of functional similarity. Following the identification of hub genes, an exploration of immune infiltration, single-cell expression, diagnostic utility, and interactions involving hub genes, RNA-binding proteins (RBPs), transcription factors (TFs), microRNAs (miRNAs), and drugs was conducted.
RESULTS: A total of 35 differentially expressed FRGs were discerned. These genes demonstrated enrichment in functions and pathways associated with ferroptosis. From the PPI network, eight hub genes were selected. Functional similarity analysis highlighted the potential pivotal roles of HMOX1 and GPX4 in azoospermia. Analysis of immune cell infiltration indicated a significant decrease in activated dendritic cells in the azoospermia group, with notable correlations between hub genes, particularly SAT1 and HMGCR, and immune cell infiltration. Unique expression patterns of hub genes across various cell types in the human testis were observed, with GPX4 prominently enriched in spermatid/sperm. Eight hub genes exhibited robust diagnostic value (AUC > 0.75). Lastly, a comprehensive hub gene-miRNA-TF-RBP-drug network was constructed.
CONCLUSIONS: In summary, our investigation unveiled eight FRDEGs associated with azoospermia, which hold potential as biomarkers for the diagnosis and treatment of azoospermia.
METHODS: A dataset related to azoospermia was retrieved from the Gene Expression Omnibus database, and FRGs were sourced from GeneCards. Ferroptosis-related differentially expressed genes (FRDEGs) were discerned. Subsequently, these genes underwent analyses encompassing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, as well as protein-protein interaction (PPI) networks and assessments of functional similarity. Following the identification of hub genes, an exploration of immune infiltration, single-cell expression, diagnostic utility, and interactions involving hub genes, RNA-binding proteins (RBPs), transcription factors (TFs), microRNAs (miRNAs), and drugs was conducted.
RESULTS: A total of 35 differentially expressed FRGs were discerned. These genes demonstrated enrichment in functions and pathways associated with ferroptosis. From the PPI network, eight hub genes were selected. Functional similarity analysis highlighted the potential pivotal roles of HMOX1 and GPX4 in azoospermia. Analysis of immune cell infiltration indicated a significant decrease in activated dendritic cells in the azoospermia group, with notable correlations between hub genes, particularly SAT1 and HMGCR, and immune cell infiltration. Unique expression patterns of hub genes across various cell types in the human testis were observed, with GPX4 prominently enriched in spermatid/sperm. Eight hub genes exhibited robust diagnostic value (AUC > 0.75). Lastly, a comprehensive hub gene-miRNA-TF-RBP-drug network was constructed.
CONCLUSIONS: In summary, our investigation unveiled eight FRDEGs associated with azoospermia, which hold potential as biomarkers for the diagnosis and treatment of azoospermia.
摘要：
目的：本研究的目的是识别与非梗阻性无精子症相关的铁死亡相关基因（FRGs），并研究相关的分子机制。
方法：从基因表达综合数据库检索与无精子症相关的数据集，FRGs来自GeneCards。识别了与铁凋亡相关的差异表达基因（FRDEG）。随后，这些基因进行了包括基因本体论和京都基因和基因组百科全书的分析，以及蛋白质-蛋白质相互作用(PPI)网络和功能相似性评估。在确定了hub基因之后，对免疫浸润的探索，单细胞表达，诊断实用程序，以及涉及中枢基因的相互作用，RNA结合蛋白（RBP），转录因子（TFs），microRNAs(miRNAs),和药物进行。
结果:共发现35个差异表达的FRG。这些基因显示了与铁凋亡相关的功能和途径的富集。从PPI网络来看，选择了八个hub基因。功能相似性分析强调了HMOX1和GPX4在无精子症中的潜在关键作用。免疫细胞浸润分析表明，无精子症组的活化树突状细胞明显减少，集线器基因之间有显著的相关性，特别是SAT1和HMGCR，和免疫细胞浸润。观察到人类睾丸中各种细胞类型的hub基因的独特表达模式，GPX4显著富含精子细胞/精子。八个hub基因表现出稳健的诊断价值(AUC>0.75)。最后,构建了一个全面的hub基因-miRNA-TF-RBP-药物网络。
结论：总之，我们的调查揭示了8个与无精子症有关的FRDEG，具有作为无精子症诊断和治疗的生物标志物的潜力。
方法：从基因表达综合数据库检索与无精子症相关的数据集，FRGs来自GeneCards。识别了与铁凋亡相关的差异表达基因（FRDEG）。随后，这些基因进行了包括基因本体论和京都基因和基因组百科全书的分析，以及蛋白质-蛋白质相互作用(PPI)网络和功能相似性评估。在确定了hub基因之后，对免疫浸润的探索，单细胞表达，诊断实用程序，以及涉及中枢基因的相互作用，RNA结合蛋白（RBP），转录因子（TFs），microRNAs(miRNAs),和药物进行。
结果:共发现35个差异表达的FRG。这些基因显示了与铁凋亡相关的功能和途径的富集。从PPI网络来看，选择了八个hub基因。功能相似性分析强调了HMOX1和GPX4在无精子症中的潜在关键作用。免疫细胞浸润分析表明，无精子症组的活化树突状细胞明显减少，集线器基因之间有显著的相关性，特别是SAT1和HMGCR，和免疫细胞浸润。观察到人类睾丸中各种细胞类型的hub基因的独特表达模式，GPX4显著富含精子细胞/精子。八个hub基因表现出稳健的诊断价值(AUC>0.75)。最后,构建了一个全面的hub基因-miRNA-TF-RBP-药物网络。
结论：总之，我们的调查揭示了8个与无精子症有关的FRDEG，具有作为无精子症诊断和治疗的生物标志物的潜力。
