三阴性乳腺癌发生及预后相关基因的筛选及功能分析

Screening and function of occurrence and prognosis-related genes in triple-negative breast cancer

目的筛选与三阴性乳腺癌(TNBC)发生及预后相关的潜在基因,并分析基因生物学功能。方法在癌症基因数据库中选取具有完整转录组测序数据和临床数据的乳腺癌患者共869例。利用加权基因共表达网络分析筛选与TNBC相关的模块基因,并对其进行基因功能和通路富集分析,构建蛋白质-蛋白质互作网络。筛选并鉴定核心基因,分析其与TNBC患者预后的关系。结果共确定11个模块,其中Blue模块与TNBC具有较高相关性。从Blue模块中获得7个核心基因,其中母体胚胎亮氨酸拉链激酶(MELK)基因是影响TNBC患者预后的潜在基因。MELK基因主要参与细胞增殖、细胞分裂和细胞周期等生物学过程。MELK基因高表达患者的总体生存率和无复发生存率均低于MELK基因低表达患者(P<0.05)。结论MELK基因在TNBC的发生发展中扮演着重要的角色,且与TNBC患者的预后密切相关。

Objective To screen potential genes related to the occurrence and prognosis of triple-negative breast cancer(TNBC),and to analyze the biological function of the genes.Methods A total of 869 breast cancer patients with complete transcriptome sequencing data and clinical data were selected from the cancer gene database.TNBC-related module genes,which were screened out by the weighted gene co-expression network analysis(WGCNA),underwent gene ontology and pathway enrichment analysis,and protein-protein interaction network was constructed.Core genes screening and identification was performed prior to analysis of their relationship with prognosis in TNBC patients.Results A total of 11 modules were identified,in which Blue module highly correlated with TNBC.Seven core genes were obtained from Blue module,in which maternal embryonic leucine zipper kinase(MELK)gene was a potential gene that affected the prognosis of TNBC patients.MELK gene was mainly involved in cell proliferation,cell division,cell cycle and other biological processes.Patients with high expression of MELK gene exhibited lower overall survival rate and recurrence-free survival rate than patients with low expression of MELK gene(P<0.05).Conclusion MELK gene plays an important role in the development and progression of TNBC,and it closely correlates with the prognosis of TNBC patients.