TICRR基因与乳腺癌发生及预后关系的研究  

Increased TICRR expression predicts poor clinical outcomes and may be a new potential therapeutic target for breast cancer

作　　者：李健[1,5] 王颜[4] 梁雷 刘阳 LI Jian;WANG Yan;LIANG Lei;LIU Yang(Department of Breast Disease,Affiliated Taian City Central Hospital of Qingdao University,Tai'an,Shandong 271000;Department of Obstetrics and Gynecology,Affiliated Taian City Central Hospital of Qingdao University,Tai'an,Shandong 271000;Department of Hepatobiliary Surgery,Affiliated Taian City Central Hospital of Qingdao University,Tai'an,Shandong 271000;Department of Applied Mathematics,College of Information Science and Engineering,Shandong Agricultural University,Tai'an,Shandong 271018;Postdoctoral Workstation,Liaocheng People's Hospital,Liaocheng,Shandong 252000)

机构地区：[1]青岛大学附属泰安市中心医院乳腺疾病诊疗部,山东泰安271000 [2]青岛大学附属泰安市中心医院妇产科,山东泰安271000 [3]青岛大学附属泰安市中心医院肝胆外科,山东泰安271000 [4]山东农业大学信息科学与工程学院应用数学系,山东泰安271000 [5]聊城市人民医院博士后工作站,山东聊城252000

出　　处：《中国现代普通外科进展》2022年第12期933-937,共5页Chinese Journal of Current Advances in General Surgery

摘　　要：目的:评价TopBP1相互作用检查点和复制调节器(TICRR)基因在乳腺癌发生和预后中的作用。方法:基于肿瘤基因组图谱(TCGA)数据库中的乳腺癌的测序和临床数据,使用Wilcoxon秩和检验确定TICRR在肿瘤组织和正常组织中的表达。使用基因集富集分析(GSEA)方法评估TICRR的生物学功能。应用Logistic分析研究TICRR表达与乳腺癌临床病理特征的相关性。采用Cox回归分析、Kaplan-Meier分析和列线图确定TICRR对乳腺癌患者临床结局的预测价值。结果:TICRR在乳腺癌组织中表达显著升高(P<0.001)。GSEA分析结果表明,TICRR表达增加主要通过促进细胞周期循环、同源重组等通路来促进肿瘤细胞增。乳腺癌组织中TICRR的高表达与年龄、临床分期、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子2(HER2)表达有关。Logistics回归分析发现TICRR表达与T分期、HER2表达呈正相关,与ER和PR表达呈负相关。Cox回归分析显示,TICRR基因表达是乳腺癌总生存率(HR:1.881,P=0.036)的独立风险因素,在无疾病进展生存期(PFI)单因素分析中是危险因素(P<0.05)。结论:TICRR基因表达增加可能通过调节细胞周期、代谢等相关通路促进乳腺癌发生,检测TICRR基因表达对评价乳腺癌预后有较高的预测价值。Objective:To explore the expression and clinical prognostic value of TICRR gene in breast cancer,we used the The Tumor Genome Atlas(TCGA)database to assess the role of TICRR in breast cancer(BC)tumorigenesis and prognosis and constructed a prognostic nomogram and validated its performance.Methods:Based on sequencing and clinical data of breast cancer(BRCA)from The Tumor Genome Atlas(TCGA)database,we determined TICRR expression between tumor and normal tissue by using Wilcoxon rank sum test.The biological function of TICRR was assessed using the gene set enrichment analysis(GSEA)method.Logistic analysis was applied to investigate the correlation between TICRR expression and clinicopathological features.Finally,Cox regression analysis,Kaplan-M eier analysis and nomogram were used to determine the predictive value of TICRR on clinical outcomes in BC patients.Results:TICRR expression was significantly elevated in BC tumors(P<0.001).GSEA results showed that main pathways such as cell cycle recycling,homologous recombination were enriched in the high expression group,and multiple metabolic pathways such as drug,arachidonic acid metabolism were enriched in the low expression group.High expression of TICRR in BC was associated with younger,higher clinical stage,positive Human epidermal growth factor 2(HER2)expression,negative estrogen receptor(ER)and progesterone receptor expression.Logistic regression analysis revealed that TICRR expression was significantly positively correlated with T stage and HER2 expression,but negatively correlated with ER and PR expression.Further Cox regression analysis showed that TICRR expression was an independent risk factor for overall survival(P=0.036)and was a risk factor in the univariate analysis of progress free interval(PFI)(P<0.05).Conclusion:Increased TICRR expression in BC may play an important role in tumorigenesis by regulating cell cycle,metabolism and other related pathways.It will be a valuable predictive biomarker for clinical prognosis of BC.

关 键 词：乳腺肿瘤 TopBP1相互作用检查点和复制调节器 预后 列线图 

分 类 号：R737.9[医药卫生—肿瘤]