Abstract：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),type Ⅰcollagen α1 chain(COL1A1),matrix metalloproteinase 2(MMP2),type Ⅲcollagen α1 chain(COL3A1),type Ⅰcollagen α2 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=0.023 00; VEGFA: HR=1.35,95%CI =1.09-1.68, P=0.005 50),and low expression of DCN was associated with poor OS(HR=0.69,95%CI=0.56-0.86, P=0.000 71).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=0.041 00; VEGFA: HR=1.39,95%CI=1.14-1.68, P=0.000 95; COL1A1: HR=1.53,95%CI=1.09-2.14, P=0.012 00; POSTN: HR=1.61,95%CI=1.16-2.24, P=0.004 20; BGN: HR=1.29,95%CI=1.07-1.57, P=0.009 20; LOX: HR=1.28,95%CI=1.06-1.55, P=0.012 00),and low expression of DCN was associated with poor DMFS(HR=0.82,95%CI=0.67-0.99, P=0.042 00).Conclusion FN1,VEGFA and DCN can be used as key biomarkers related to the prognosis of breast cancer brain metastasis.
邵明涛； 王兴； 李伟文. 基于生物信息学对乳腺癌脑转移生物标志物的筛选与鉴定[J]. 中国当代医药, 2021, 28(22): 8-11转15.
SHAO Ming-tao； WANG Xing ；LI Wei-wen. Screening and identification of biomarkers for breast cancer brain metastasis based on bioinformatics. 中国当代医药, 2021, 28(22): 8-11转15.
Bray F，Ferlay J，Soerjomataram I，et al.Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin，2018，68（6）：394-424.
Bendell JC，Domchek SM，Burstein HJ，et al.Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma[J].Cancer，2003，97（12）：2972-2977.
Szklarczyk D，Gable AL，Lyon D，et al.STRING v11：protein-protein association networks with increased coverage，supporting functional discovery in genome-wide experimental datasets[J].Nucleic Acids Res，2019，47（D1）：D607-D613.
[6]
Chin CH，Chen SH，Wu HH，et al.cytoHubba：identifying hub objects and sub-networks from complex interactome[J].BMC Syst Biol，2014，8（Suppl 4）：S11.
[7]
Wang H，Liu J，Li J，et al.Identification of gene modules and hub genes in colon adenocarcinoma associated with pathological stage based on WGCNA analysis[J].Cancer Genet，2020，242：1-7.
[8]
Lanczky A，Nagy A，Bottai G，et al.miRpower：a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients[J].Breast Cancer Res Treat，2016，160（3）：439-446.
[9]
Yamamura J，Masuda N，Yasojima H，et al.Clinicopathological Factors Related to the Prognosis of Metastatic Breast Cancer Patients after Development of Brain Metastasis[J].Breast Care （Basel），2015，10（6）：387-392.
[10]
Gaedcke J，Traub F，Milde S，et al.Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer[J].Mod Pathol，2007，20（8）：864-870.
Niwinska A，Murawska M，Pogoda K.Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases[J].Cancer，2010，116（18）：4238-4247.
[12]
Loganathan J，Jiang J，Smith A，et al.The mushroom Ganoderma lucidum suppresses breast-to-lung cancer metastasis through the inhibition of pro-invasive genes[J].Int J Oncol，2014，44（6）：2009-2015.
[13]
Razak NA，Abu N，Ho WY，et al.Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest，anti-angiogenesis and induction of apoptosis[J].Sci Rep，2019，9（1）：1514.
[14]
Sun H.Identification of key genes associated with gastric cancer based on DNA microarray data[J].Oncol Lett，2016，11（1）：525-530.
[16]
Tang Z，Yang Y，Zhang J，et al.Quantitative Proteomic Analysis and Evaluation of the Potential Prognostic Biomarkers in Cholangiocarcinoma[J].J Cancer，2019，10（17）：3985-3999.
[17]
Kalikawe R，Baba Y，Nomoto D，et al.Lysyl oxidase impacts disease outcomes and correlates with global DNA hypomethylation in esophageal cancer[J].Cancer Sci，2019，110（12）：3727-3737.
[18]
Miller BW，Morton JP，Pinese M，et al.Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly：inhibition of LOX abrogates metastasis and enhances drug efficacy[J].EMBO Mol Med，2015，7（8）：1063-1076.
[19]
Liu Y，Wang G，Liang Z，et al.Lysyl oxidase：A colorectal cancer biomarker of lung and hepatic metastasis[J].Thorac Cancer，2018，9（7）：785-793.
京公网安备 11010502046607号