三阴性乳腺癌组织中HK3表达及临床意义

Expression and clinical significance of HK3 in triple-negative breast cancer tissues

目的评估三阴性乳腺癌(TNBC)组织中己糖激酶3(HK3)表达及临床意义,并初步探讨HK3在TNBC中可能的作用机制。方法收集全球范围内乳腺癌组织的基因芯片、RNA-seq数据集。绘制SMD森林图,评估HK3的表达水平。绘制汇总受试者操作特征(SROC)曲线并计算灵敏度、特异度。使用Cox回归分析评估HK3对TNBC患者预后的预测能力。此外,通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)及Reactome富集对HK3相关通路分析,探讨HK3在TNBC中的可能机制。结果TNBC组织HK3表达水平显著高于正常乳腺组织(SMD=0.58),高表达的HK3鉴别TNBC与非癌乳腺组织的灵敏度为0.81。同时TNBC组织中的HK3表达水平也显著高于非TNBC组织(SMD=0.48),其区分TNBC与非TNBC乳腺组织的灵敏度为0.79。TNBC组织中HK3高表达组较HK3低表达组有更长的总生存期和无进展生存期(均P<0.05)。HK3表达相关的基因可能参与免疫系统调控的通路。结论高表达的HK3可促进TNBC的发生,其表达水平在TNBC中具有较高的诊断和预后评估价值。HK3在TNBC中有可能通过影响免疫系统调控发挥作用。

Objective To assess the expression level and clinical significance of HK3 in triple-negative breast cancer(TNBC)tissues.Methods Gene microarray and RNA-seq data sets of breast cancer tissues were collected from databases of gene expression omnibus(GEO),the cancer genome atlas(TCGA),sequence read archive(SRA),ArrayExpress,and molecular taxonomy of Breast Cancer International Consortium(METABRIC).SMD forest plots were generated to assess the expression levels of HK3.Summary receiver operating characteristic(SROC)curves were plotted,and sensitivity and specificity of HK3 to distinguish TNBC from non-cancerous breast tissues were calculated.The predictive ability of HK3 on the prognosis of TNBC patients was assessed using Cox regression analysis.The action mechanisms of HK3 in TNBC were explored by analysis of HK3-related pathways based on gene ontology(GO),Kyoto encyclopedia of genes and genomes(KEGG)and Reactome enrichment.Results HK3 expression level in TNBC tissues was significantly higher than that in normal breast tissues(SMD=0.58),and the sensitivity of the highly expressed HK3 to distinguish TNBC from non-cancerous breast tissues was 0.81.The expression level of HK3 in TNBC tissues was significantly higher than that in non-TNBC tissues(SMD=0.48),and the sensitivity in differentiating between TNBC and non-TNBC tissues was 0.79.However,TNBC patients with high HK3 expression had a longer overall survival(OS)and progression-free survival(PPS)than those with low HK3 expression(both P<0.05).Genes associated with HK3 expression might be involved in immune system-regulating pathways.Conclusion HK3 is highly expressed in TNBC patients and promotes the cancer development through regulating pathway of immune system.HK3 may have diagnostic and prognostic value for TNBC patients.