摘要
目的寻找与乳腺癌脑转移预后相关的关键生物标志物。方法从GEO数据库检索获得的微阵列数据集GSE125989,并采用GEO2R工具来筛选相关差异表达基因。使用STRING数据库分析差异基因的蛋白质-蛋白质相互作用,使用Cytoscape软件进行可视化处理并筛选出关键的生物标志物。使用Kaplan-Meier生存分析数据库确定所筛选出的关键生物标志物的预后潜力。结果本研究筛选出311个上调差异基因和104个下调差异基因,并筛选出了10个关键基因,包括纤维连接蛋白1(FN1)、血管内皮生长因子A(VEGFA)、Ⅰ型胶原蛋白α1链(COL1A1)、基质金属蛋白酶2(MMP2)、Ⅲ型胶原蛋白α1链(COL3A1)、Ⅰ型胶原蛋白α2链(COL1A2)、骨膜蛋白(POSTN)、核心蛋白聚糖(DCN)、双糖链蛋白聚糖(BGN)和赖氨酰氧化酶(LOX)。通过Kaplan-Meier生存分析发现,FN1和VEGFA高表达,均与不良的总生存期(OS)相关(FN1:HR=1.28,95%CI=1.03~1.59,P=0.02300;VEGFA:HR=1.35,95%CI=1.09~1.68,P=0.00550),而低表达DCN与不良OS相关(HR=0.69,95%CI=0.56~0.86,P=0.00071)。FN1、VEGFA、COL1A1、POSTN、BGN和LOX高表达,均与不良的无远处转移生存(DMFS)相关(FN1:HR=1.22,95%CI=1.01~1.48,P=0.04100;VEGFA:HR=1.39,95%CI=1.14~1.68,P=0.00095;COL1A1:HR=1.53,95%CI=1.09~2.14,P=0.01200;POSTN:HR=1.61,95%CI=1.16~2.24,P=0.00420;BGN:HR=1.29,95%CI=1.07~1.57,P=0.00920;LOX:HR=1.28,95%CI=1.06~1.55,P=0.01200),而DCN低表达与不良的DMFS相关(HR=0.82,95%CI=0.67~0.99,P=0.04200)。结论FN1、VEGFA和DCN可作为乳腺癌脑转移预后相关的关键生物标志物。
Objective To find the key biomarkers related to the prognosis of breast cancer brain metastasis.Methods The microarray data set GSE125989 was retrieved from the GEO database,and the GEO2R tool was used to screen the relevant differentially expressed genes.The STRING database was used to analyze the protein-protein interactions of the differential genes,and the Cytoscape software was used for visualization and screening of key biomarkers.The Kaplan-Meier survival analysis database was used to determine the prognostic potential of the key biomarkers screened.Results In this study,311 differentially up-regulated genes and 104 differentially down-regulated genes were screened,and 10 key genes were screened,including fibronectin 1(FN1),vascular endothelial growth factor A(VEGFA),typeⅠcollagenα1 chain(COL1A1),matrix metalloproteinase 2(MMP2),typeⅢcollagenα1 chain(COL3A1),typeⅠcollagenα2 chain(COL1A2),periosteal protein(POSTN),decorin(DCN),biglycan(BGN)and lysyl oxidase(LOX).Kaplan-Meier survival analysis showed that high expressions of FN1 and VEGFA were associated with poor overall survival(OS)(FN1:HR=1.28,95%CI=1.03-1.59,P=0.02300;VEGFA:HR=1.35,95%CI=1.09-1.68,P=0.00550),and low expression of DCN was associated with poor OS(HR=0.69,95%CI=0.56-0.86,P=0.00071).High expressions of FN1,VEGFA,COL1A1,POSTN,BGN,and LOX were associated with poor distant metastasis-free survival(DMFS)(FN1:HR=1.22,95%CI=1.01-1.48,P=0.04100;VEGFA:HR=1.39,95%CI=1.14-1.68,P=0.00095;COL1A1:HR=1.53,95%CI=1.09-2.14,P=0.01200;POSTN:HR=1.61,95%CI=1.16-2.24,P=0.00420;BGN:HR=1.29,95%CI=1.07-1.57,P=0.00920;LOX:HR=1.28,95%CI=1.06-1.55,P=0.01200),and low expression of DCN was associated with poor DMFS(HR=0.82,95%CI=0.67-0.99,P=0.04200).Conclusion FN1,VEGFA and DCN can be used as key biomarkers related to the prognosis of breast cancer brain metastasis.
作者
邵明涛
王兴
李伟文
SHAO Ming-tao;WANG Xing;LI Wei-wen(Department of Thyroid and Breast Surgery,Jiangmen Central Hospital,Guangdong Province,Jiangmen529000,China)
出处
《中国当代医药》
CAS
2021年第22期8-10,15,F0003,共5页
China Modern Medicine
基金
广东省江门市医疗卫生领域科技计划项目(2019A088)。
