背景:据报道,铁凋亡在各种人类癌症中具有治疗潜力。在本研究中,我们探索了表达,FK506结合蛋白3(FKBP3)在肺腺癌(LUAD)进展中的临床意义及分子机制。
方法:进行Cox回归以从TCGA获得与LUAD数据集中差异表达基因(DEGs)相关的预后。我们还从GeneCards下载了与铁凋亡相关的基因数据集。进行维恩图以找到相交基因,并且通过分析Top10相交基因的诊断和预后价值来选择FKBP3作为靶基因。此外,我们进行了单因素和多因素分析,以评估临床病理因素和生存率之间的关联.进行GO/KEGG和GSEA分析以探讨FKBP3在LUAD进展中的功能。通过STRING数据库进行蛋白质-蛋白质相互作用(PPI)网络,并选择top10hub基因。最后,通过ssGSEA分析探讨FKBP3与免疫浸润的关系。
结果:首先,获得了184个与LUAD和铁凋亡预后相关的基因。发现FKBP3与LUAD患者的低总生存率显著相关。免疫组织化学染色成果显示FKBP3在LUAD组织中高度定位于细胞的胞浆和胞膜。PPI网络分析结果表明,HDAC1、YY1、HDAC2、MTOR、PSMA3,PIN1,NCL,C14orf166、PIN4和LARP6是top10hub基因。此外,spearman分析结果显示,FKBP3的表达与Th2细胞和T辅助细胞的丰度呈正相关。
结论:高水平的FKBP3与LUAD患者预后不良相关,这也抑制了LUAD组织中的免疫浸润。此外,FKBP3参与调节LUAD患者的铁凋亡过程。因此,FKBP3在LUAD进展中具有促进肿瘤生长的作用,可能参与调节铁细胞凋亡和免疫浸润。
BACKGROUND: Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the molecular mechanism of FK506 binding protein 3 (FKBP3) in the progression of lung adenocarcinoma (LUAD).
METHODS: Cox regression was performed to obtain the prognosis related to differentially expressed genes (DEGs) in LUAD datasets from TCGA. We also downloaded the ferroptosis-related gene datasets from GeneCards. Venn diagram was performed to find the intersecting genes and FKBP3 was selected as the targeted gene by analyzing the diagnostic and prognostic values of Top10 intersecting genes. Moreover, univariate and multivariate analyses were performed to evaluate the association between clinicopathological factors and survival rates. GO/KEGG and GSEA analysis was performed to explore the function of FKBP3 in LUAD progression. Protein-protein interaction (PPI) network was performed via STRING database and the top10 hub genes were selected. Finally, the relationship between FKBP3 and immune infiltration was explored by ssGSEA analysis.
RESULTS: Firstly, 184 genes associated with the prognosis of LUAD and ferroptosis were obtained. FKBP3 was found to be significantly associated with a poor overall survival rate of LUAD patients. Immunohistochemical staining results showed that FKBP3 was highly located in cytoplasm and membrane of cells in LUAD tissues. PPI network analysis results showed that HDAC1, YY1, HDAC2, MTOR, PSMA3, PIN1, NCL, C14orf166, PIN4, and LARP6 were the top10 hub genes. Furthermore, spearman analysis results showed that the expression of FKBP3 was positively correlated with the abundance of Th2 cells and T helper cells.
CONCLUSIONS: High level of FKBP3 was associated with poor prognostic outcomes of LUAD patients, which also inhibited immune infiltration in LUAD tissues. Additionally, FKBP3 was involved in regulating the ferroptosis process in LUAD patients. Thus, FKBP3 possessed the tumor promotion role might be involving in regulating ferroptosis and immune infiltration in LUAD progression.