NUF2基因在乳腺癌中的表达及临床意义

Expression of NUF2 in breast cancer and its clinical significance

目的探讨细胞分裂相关基因NUF2在乳腺癌的表达及临床意义。方法利用Oncomine数据库检测NUF2在乳腺癌组织中的表达情况,利用Kaplan-Meier Plotter数据库分析NUF2表达与乳腺癌患者总生存期和无复发生存期的关系,利用GEO数据库及GSEA分析NUF2对基因集富集的影响。利用String数据库分析与NUF2相关的蛋白并通过TIMER数据库验证NUF2表达情况与BUB1、MAD2L1、MYC表达情况的相关性。利用q-PCR验证在8对乳腺癌组织与配对的癌旁正常乳腺组织中,NUF2的mRNA表达情况。结果与正常乳腺组织相比,NUF2在乳腺癌中高表达(P<0.001),且高表达组比低表达组具有较短的总生存期(HR=1.52,P=0.015)和无复发生存期(HR=1.85,P<0.001)。NUF2高表达组的乳腺癌样本主要富集在细胞周期、P53、G2/M、DNA修复、MYC和PI3K-AKT-MTOR信号通路,这些通路主要与肿瘤的增殖、侵袭、转移和干性相关。结合String、基因集富集以及TIMER的结果,NUF2可能与BUB1、MAD2L1、MYC直接相互结合作用,促进乳腺癌的进展。q-PCR实验结果显示在8对配对乳腺癌组织中,6例癌组织中NUF2表达上调,2例癌组织中NUF2表达下调。结论 NUF2基因在乳腺癌中高表达,其表达水平对预测乳腺癌患者的预后具有重要意义。

Objective To investigate the expression of the cell division-associated gene NUF2 in breast cancer and its clinical significance.Methods The expression of NUF2 in breast cancer tissues was analyzed using Oncomine database.The relationship between the expression of NUF2 and the prognosis of breast cancer was analyzed using the Kaplan-Meier Plotter database.Gene set enrichment analysis(GSEA)and GEO database were used to investigate the effect of NUF2 on gene enrichment.The String database was utilized to analyze the proteins associated with NUF2.The TIMER database was analyzed to assess the correlations of NUF2 with BUB1,MAD2 L1 and MYC.The expressions of NUF2 mRNA in 8 pairs of breast cancer tissues and adjacent tissues were verified by q-PCR.Results Compared with that in normal breast tissue,NUF2 was significantly overexpressed in breast cancer(P<0.001).The overall survival time(HR=1.52,P=0.015)and the recurrence-free survival time(HR=1.85,P=3.2 e-14)of the patients with high NUF2 expression were significantly shorter than those of patients with low NUF2 expression.In patients with high NUF2 expression,the enriched genes were involved mainly in cell cycle,P53,G2/M,DNA repair,MYC,and PI3 K-AKT-MTOR signaling pathways,which were associated with tumor proliferation,invasion,metastasis and stemness.Combination of the results of String database,gene enrichment and TIMER database analyses suggested that NUF2 interacted directly with BUB1,MAD2 L1,and MYC,which could promote the progression of breast cancer.The results of q-PCR showed that NUF2 expression was up-regulated in 6 cancer tissues and down-regulated in2 cancer tissues.Conclusion NUF2 gene is overexpressed in breast cancer,and its expression level is important in predicting the prognosis of breast cancer.