三阴乳腺癌中MIR892B和CDK1的基因拷贝数变异与患者恶性进展的相关性分析

Correlation between gene copy number variation of MIR892B and CDK1 and malignant progression in triple negative breast cancer

目的探讨三阴乳腺癌(TNBC)中MIR892B和CDK1的基因拷贝数变异(CNV)与患者恶性进展的相关性。方法从癌症基因组图谱数据库(TCGA)中,获得153例TNBC患者的全基因组CNV数据和预后数据。GISTIC2.0软件分析肿瘤中全基因组CNV情况,筛选出CNV的热点基因,并与患者5年进展预后进行相关性分析。收集整理2012年1月至2015年12月在江门市中心医院就诊的88例TNBC患者资料,荧光定量PCR检测肿瘤组织中MIR892B和CDK1基因CNV,并分析其与患者预后的相关性。结果TCGA中全基因组区段的分析显示,3p26.1、10q21.2和19q12在32例5年有进展患者肿瘤组织中明显扩增,6p21.1、11q13.4和Xq27.3在27例无进展的患者肿瘤组织中明显扩增;4p13和12q24.32在有进展患者肿瘤组织中明显缺失,13q22.2和19p13.3在无进展患者肿瘤组织中有明显缺失。在TCGA及江门市中心医院样品中,仅有MIR892B(Xq27.3)的扩增情况与TNBC患者5年发生进展事件相关,且MIR892B(Xq27.3)的非扩增或CDK1(10q21.2)扩增的TNBC患者5年生存预后较差(P<0.001)。结论TNBC中MIR892B和CDK1的基因CNV与患者恶性进展相关。

Objective To investigate the correlation between MIR892B and CDK1 gene copy number variation(CNV)and malignant progression in triple-negative breast cancer(TNBC).Methods The whole genome CNV data and prognosis data in 153 cases of TNBC were obtained from the Cancer Genome Atlas(TCGA).The GISTIC2.0 software was used to analyze the whole genome CNV in the tumor for screening out the hotspot genes of CNV,and conducting the correlation analysis on the progress and prognosis of the patients within 5 years.The data in 88 cases of TNBC in the Jiangmen Municipal Central Hospital from January 2012 to December 2015 were collected and arranged.The fluorescence quantitative PCR was used to detect CNV of MIR892B and CDK1 genes in tumor tissues,and their correlation with the prognosis of the patients was analyzed.Results The whole genome segments analysis in TCGA showed that 3p26.1,10q21.2 and 19q12 were significantly amplified in the tumor tissues of 32 patients with progress within 5 years,while 6p21.1,11q13.4 and Xq27.3 were significantly amplified in the tumor tissues of 27 patients with non-progress.4p13 and 12q24.32 were significantly deleted in the tumor tissues of the patients with progression,while 13q22.2 and 19p13.3 were significantly deleted in the tumor tissues of the patients with non-progress.In TCGA and the samples of the Jiangmen Municipal Central Hospital,only the amplification situation of MIR892B(Xq27.3)was correlated with the progression events of TNBC patients within 5 years,moreover the five-year survival prognosis of the TNBC patients with non-amplified MIR892B(Xq27.3)or CDK1(10q21.2)amplification was worse(P<0.001).Conclusion CNV of MIR892B and CDK1 in TNBC is correlated with the malignant progression of the patients.