【摘要】 目的研究6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶4 (PFKFB4)的表达水平与宫颈癌患者临床病理特征和预后的关系,并探讨PFKFB4在宫颈癌进展中的调控网络。方法利用Linked Omics数据平台分析PFKFB4的表达与宫颈癌患者临床病理特征及预后的关系。利用Linked Omics的Link Finder模块Gene Set Enrichment Analysis (GSEA)对差异相关基因进行基因本体(GO)[细胞成分(CC),生物过程(BP)和分子功能(MF)]分析。KEGG信号通路分析激酶靶标富集,miRNA靶标富集和转录因子靶标富集。cBioPortal用于分析PFKFB4在宫颈癌中的变异频率和类型。Gene MANIA用于分析与PFKFB4存在相互作用的基因以及主要涉及的功能。结果 PFKFB4与宫颈癌的T分期、N分期和M分期显著相关;T分期越高、有淋巴结转移(N1)、伴有远处转移(M1)者PFKFB4表达量越高;PFKFB4高表达患者的总生存显著差于低表达患者(P=0.002);GO分析提示PFKFB4相关基因与蛋白结合、离子结合、核酸结合、水解酶活动、转移酶活动等相关;KEGG信号通路富集分析则发现,PFKFB4及相关基因在宫颈癌中主要参与了缺氧诱导因子HIF1信号通路、糖酵解/糖再生信号通路、果糖和甘露糖代谢通路等;GSEA分析显示,MK2PK1、CHEK1、miR-200a、miR-18a、HIF1、AP1与PFKFB4的表达显著相关;cBioPortal分析显示,PFKFB4在宫颈癌中主要变异形式为m RNA高表达,但是突变频率较低。结论 PFKFB4是宫颈癌一个潜在的预后标记物。通过数据挖掘揭示了PFKFB4的潜在调控网络信息,为进一步研究PFKFB4在宫颈癌中的作用奠定基础。更多还原

【Abstract】 Objective To investigate the relationship between the expression level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4(PFKFB4) and the clinicopathological features and prognosis of cervical cancer, and to explore the regulatory network of PFKFB4 in the progression of cervical cancer. Methods The correlation between the expression of PFKFB4 and the clinicopathological characteristics and prognosis of cervical cancer patients was analyzed using the Linked Omics data platform. Gene ontology [cellular component(CC), biological process(BP), and molecular function(MF)] analysis of differentially related genes was performed using the Link Finder module Gene Set Enrichment Analysis(GSEA) of Linked Omics. KEGG signaling pathway was used to analyze kinase target enrichment,miRNA target enrichment, and transcription factor target enrichment. c BioPortal was used to analyze the variation frequency and type of PFKFB4 in cervical cancer. Gene MANIA was used to analyze genes that interact with PFKFB4 and the main functions involved. Results PFKFB4 was significantly correlated with T, N and M stages of cervical cancer.PFKFB4 was significantly higher in patients with higher T stage, patients with lymph node metastasis(N1), and patients with distant metastasis(M1). Overall survival was significantly worse in patients with high PFKFB4 expression than in patients with low PFKFB4 expression(P=0.002). GO analysis suggested that PFKFB4 related genes were related to protein binding, ion binding, nucleic acid binding, hydrolase activity, and transferase activity. Enrichment analysis of KEGG signaling pathway found that PFKFB4 and related genes were mainly involved in the hypoxia-inducible factor HIF1 signaling pathway, glycolysis/sugar regeneration signaling pathway, fructose and mannose metabolism pathways in cervical cancer. GSEA analysis showed that MK2 PK1, CHEK1, miR-200 a, miR-18 a, HIF1, and AP1 were significantly correlated with the expression of PFKFB4. cBioPortal analysis showed that the main variant form of PFKFB4 in cervical cancer was high mRNA expression, but the mutation frequency was low. Conclusion PFKFB4 is a potential prognostic marker for cervical cancer. Through data mining, the potential regulatory network information of PFKFB4 is revealed, which lays a foundation for further research on the role of PFKFB4 in cervical cancer.更多还原