GLIS3蛋白在三阴性乳腺癌中的表达及其对患者预后的影响  

Expression of GLIS3 protein in triple negative breast cancer and its influence on prognosis of patients

作　　者：李晨浩 刘月平[2] 李春晓[3,4,5] 崔国忠[1] 黄徐晨 张乙 张国宇 耿翠芝[3,4,5] LI Chenhao;LIU Yueping;LI Chunxiao;CUI Guozhong;HUANG Xuchen;ZHANG Yi;ZHANG Guoyu;GENG Cuizhi(Second Department of Thyroid and Breast Surgery,Cangzhou Central Hospital,Cangzhou,Hebei Province,061000;Department of Pathology,Fourth Hospital of Hebei Medical University,Shijiazhuang,Hebei Province,050000,China;Diagnostic and Therapeutic Center for Breast Diseases,Fourth Hospital of Hebei Medical University,Shijiazhuang,Hebei Province,050000,China;Hebei Provincial Key Laboratory of Molecular Medicine of Breast Cancer,Fourth Hospital of Hebei Medical University,Shijiazhuang,Hebei Province,050000,China;Hebei Provincial Key Laboratory of Tumor Prevention and Precise Diagnosis and Treatment,Fourth Hospital of Hebei Medical University,Shijiazhuang,Hebei Province,050000,China)

机构地区：[1]沧州市中心医院甲乳外二科,河北沧州061000 [2]河北医科大学第四医院病理科,石家庄050000 [3]河北医科大学第四医院乳腺中心,石家庄050000 [4]河北医科大学第四医院河北省乳腺癌分子医学重点实验室,石家庄050000 [5]河北医科大学第四医院河北省肿瘤预防和精准诊疗重点实验室,石家庄050000

出　　处：《陆军军医大学学报》2024年第13期1553-1560,共8页Journal of Army Medical University

基　　金：河北省自然科学基金(H2020206199)。

摘　　要：目的观察GLIS3蛋白在三阴性乳腺癌(triple negative breast cancer,TNBC)组织中的表达水平,分析其与三阴性乳腺癌患者预后的关系。方法运用生物信息学方法分析基因表达综合数据库(Gene Expression Omnibus,GEO)中GLIS3的表达水平;根据DNA芯片数据,采用Kaplan-Meier生存曲线分析GLIS3的表达对患者生存率的影响。通过整群随机抽样法选取2014年1-12月在河北医科大学第四医院乳腺中心就诊并经病理确诊为TNBC的患者125例。纳入组织标本完好、病历资料完备以及随访资料完全的53例患者。通过免疫组化染色分析GLIS3在TNBC以及癌旁乳腺组织中的表达,同时分析GLIS3蛋白在乳腺癌组织中的表达与乳腺癌患者的年龄、月经周期、肿瘤大小、临床阶段、组织学评级、病理种类、腋窝淋巴结转移、脉管瘤栓、TP53、Ki-67等临床病理学参数之间的联系。利用Kaplan-Meier生存曲线分析GLIS3对三阴性乳腺癌患者的无病生存期和总生存期的影响。利用Cox回归模型分析影响三阴性乳腺癌患者预后的风险因素。结果GSE76275数据库解析结果发现,GLIS3在TNBC中的表达高于癌旁组织(P<0.05)。与癌旁乳腺组织比较,TNBC组织中GLIS3蛋白表达明显升高(P<0.05)。在肿瘤分期较高、体积较大的患者中GLIS3的表达显著升高(P<0.05)。Cox回归模型的单因素分析发现,三阴性乳腺癌患者的无病生存期与其淋巴结转移、TNM分期以及GLIS3的表达量相关(P<0.05);单因素和多因素分析结果均显示,三阴性乳腺癌患者的总生存期与TNM分期相关(P<0.05)。GLIS3高表达的患者,无病生存期明显低于GLIS3低表达的患者(P<0.05),而总生存期与GLIS3低表达的患者差异无统计学意义。结论GLIS3蛋白在TNBC组织中高表达,肿瘤大小和TNM分期与GLIS3的高表达有关,GLIS3蛋白高表达提示患者预后不良、无病生存率低。Objective To observe the expression of GLIS3 in triple negative breast cancer(TNBC)and analyze its relationship with the prognosis of TNBC patients.Methods Bioinformatic analysis was applied to analyze the expression level of GLIS3 in Gene Expression Omnibus(GEO).Kaplan-Meier survival curve was plotted to evaluate the impact of GLIS3 expression on the survival rate of patients based on DNA chip data.A total of 125 patients pathologically diagnosed as TNBC in the Fourth Hospital of Hebei Medical University from January to December 2014 were enrolled by cluster random sampling.Among them,53 patients had complete tissue specimens,medical records and follow-up data.Immunohistochemical assay was used to detect the expression of GLIS3 in TNBC and adjacent tissues to tumors,while the relationships between GLIS3 protein expression in breast cancer tissues and clinicopathological parameters such as age,menstrual status,tumor size,clinical stage,histological grade,pathological type,axillary lymph node metastasis,vascular tumor thrombus,and expression of TP53 and Ki-67 were analyzed.Kaplan-Meier survival curve was plotted to analyze the effect of GLIS3 on the overall and disease-free survival of TNBC patients.Cox regression model was established to identify the risk factors impacting the prognosis of the patients.Results Analysis of GEO data showed that the expression of GLIS3 in TNBC was significantly higher than that in paracancer tissues(P<0.05).The expression of GLIS3 was notably higher in the TNBC tissue than the adjacent tissue to tumor(P<0.05).A marked augmentation of GLIS3 expression was observed in both the advanced and larger-sized tumors(P<0.05).Univariate analysis of Cox regression model revealed that lymph node metastasis,TNM stage and GLIS3 expression were all related to disease-free survival of TNBC patients(P<0.05).Univariate and multivariate analyses displayed that TNM stage was related to the overall survival of TNBC patients(P<0.05).The patients with high expression of GLIS3 had significant shorter diseas

关 键 词：三阴性乳腺癌 GLIS3 生存率 预后 

分 类 号：R394.3[医药卫生—医学遗传学] R730.7[医药卫生—基础医学] R737.9