ASPM基因在乳腺癌中的表达及临床意义

Expression of ASPM in Breast Cancer and Its Clinical Significance

目的研究有丝分裂相关基因ASPM(abnormal spindle microtubule assembly)在乳腺癌中的表达及临床意义,并探讨ASPM作用机制。方法利用Oncomine数据库检测ASPM在乳腺癌组织中的表达情况,采用GSE3494数据集和Kaplan-Meier在线分析ASPM表达与乳腺癌患者的预后关系,并结合TCGA数据库分析ASPM表达与临床病理指标的相关性。利用GSE3494数据集进行基因富集分析(GSEA)预测ASPM相关通路。利用String数据库分析与ASPM相关的蛋白并通过TIMER数据库验证。利用RT-qPCR验证在13对乳腺癌组织与配对的癌旁组织中ASPM的表达情况。结果与正常乳腺组织比较,ASPM在乳腺癌组织中高表达,且高表达组具有较短的总生存期(HR=1.71,P=0.000)。GSE3494和TCGA数据库分析发现ASPM表达与ER、PR水平显著相关(P=0.000),TCGA数据库分析结果显示ASPM表达还跟年龄(P=0.002)以及TNM分期中的T分期(P=0.000)和N分期(P=0.030)显著相关。ASPM高表达样本主要富集在细胞周期、氧化磷酸化、DNA修复、错配修复、剪接体和蛋白酶体等基因集(P<0.01),结合String以及TIMER的结果,ASPM可能与BUB1、CCNA2、TTK、CDC20、CDK1相互结合作用,促进乳腺癌的发生、发展。RT-qPCR结果显示,ASPM在乳腺癌组织中表达上调。结论ASPM基因在乳腺癌组织中高度表达,并与临床病理指标相关,可作为预测乳腺癌预后的标志物进一步研究。

Objective To investigate the expression and clinicopathological significance of ASPM in breast cancer and to predict the possible mechanism of ASPM.Methods The expression of ASPM in breast cancer tissues was detected by Oncomine database.The relationship between ASPM expression and the prognosis of breast cancer was analyzed by GSE3494 dataset and Kaplan-Meier Plotter,and the correlation between ASPM expression and clinicopathological indicators was analyzed by TCGA database.GSE3494 dataset were used to predict ASPM related pathways using gene set enrichment analysis(GSEA).The ASPM-related proteins were analyzed using the String database and verified by the TIMER database.The expression of ASPM mRNA in 13 pairs of breast cancer tissues and matched paracancerous tissues were verified by RT-qPCR.Results Compared with normal breast tissues,ASPM was overexpressed in breast cancer tissues,and the high expression group showed a poor overall survival(HR=1.71,P=0.000).The expression of ASPM was significantly correlated with ER and PR levels(P=0.000)both in GSE3494 dataset and TCGA database,which was also significantly associated with age(P=0.002)and T stage(P=0.000)and N stage(P=0.030)in TCGA database.High expression of ASPM samples were mainly enriched in cell cycle,oxidative phosphorylation,DNA replication,mismatch repair,spliceosome and proteasome gene sets(P<0.01).Combined with the results of String and TIMER database,ASPM may interact with BUB1,CCNA2,TTK,CDC20,and CDK1,which could promote the development of breast cancer.RT-qPCR results showed that the expression of ASPM gene was overexpressed in breast cancer tissues.Conclusion ASPM is highly expressed in breast cancer tissues and is associated with multiple clinicopathological indicators,which could be further studied as a biomarker for predicting the prognosis of breast cancer.