HAX1及VEGFA表达与脑胶质瘤预后的相关性及临床价值  

Expression and clinical significance of HAX1 and VEGFA in human glioma

作　　者：王燕[1] 夏小鹏 何鑫 张曙[1] WANG Yan;XIA Xiao-peng;HE Xin;ZHANG Shu(Department of Pathology,Affiliated Hospital of Nantong University,Nantong 226006,China;Department of Orthopedics,Nantong Hospital of Traditional Chinese Medicine,Nantong 226007,China)

机构地区：[1]南通大学附属医院病理科,南通226006 [2]江苏省南通市中医院骨科,南通226007

出　　处：《临床与实验病理学杂志》2023年第1期29-36,共8页Chinese Journal of Clinical and Experimental Pathology

基　　金：南通市科技局项目(JCZ19120);南通大学临床医学专项(2019JZ016)。

摘　　要：目的探讨造血细胞特异蛋白1相关蛋白X1(hematopoietic cell specific protein 1-associated protein X1,HAX1)和血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)在脑胶质瘤中的表达及相关性,以及与患者术后生存时间、预后的关系。方法UALCAN数据库分析多形性胶质母细胞瘤(glioblastoma multiforme,GBM)组织中HAX1及VEGFA mRNA的表达水平;GEPIA数据库分析GBM组织中HAX1与VEGFA表达的相关性;qRT-PCR法检测30例脑胶质瘤及12例正常脑组织中HAX1及VEGFA mRNA的表达;组织芯片结合免疫组化法检测214例脑胶质瘤组织及86例正常脑组织中HAX1和VEGFA蛋白表达水平,分析两种蛋白表达的相关性及两者与脑胶质瘤临床病理特征及患者预后的关系;GEPIA数据库进一步分析两者表达与胶质瘤患者预后的相关性。结果数据库分析结果显示,HAX1和VEGFA mRNA在GBM组织中均高表达(P=3.874100E-02,P=1.62436730732907E-12),且两者在脑胶质瘤中表达呈正相关(r=0.14,P=0.00039);qRT-PCR结果显示,HAX1(1.66±0.40)和VEGFA(2.75±0.73)mRNA在脑胶质瘤组织中均高表达(t=4.744,P<0.0001;t=8.263,P<0.0001);免疫组化结果显示,与正常脑组织相比,HAX1(67.8%,145/214)和VEGFA(72.0%,154/214)蛋白在脑胶质瘤组织中的阳性率更高(χ^(2)=29.174,P<0.05;χ^(2)=33.477,P<0.05),且两者表达呈正相关(r=0.593,P<0.05);HAX1和VEGFA蛋白表达均与行为状态评分(karnofsky performance status,KPS)、组织分化程度、WHO分级、p53及Ki-67蛋白表达密切相关(P<0.05);生存分析显示,HAX1阳性及VEGFA阳性患者的总生存率(5.5%、6.5%)明显低于HAX1阴性患者(62.3%、68.3%)(P<0.001),且两者均阳性的患者总生存率(4.6%)更低(P<0.001);预后分析显示,HAX1蛋白阳性(HR=1.746,P=0.026)、VEGFA蛋白阳性(HR=2.760,P<0.001)、组织中+低分化(HR=3.097,P=0.034)、WHO高分级(HR=1.533,P=0.005)及Ki-67蛋白阳性(HR=1.827,P=0.011)是患者预后的独立危险因素。GEPIA数据库分析结果亦显示,HAX1(HR=1.4,P=0.Purpose To investigate the expression levels and correlation of hematopoietic cell specific protein 1-associated protein X1(HAX1)and vascular endothelial growth factor A(VEGFA)in glioma,and their relationships with the postoperative survival time and prognosis of patients.Methods The expression levels of HAX1 and VEGFA mRNA in glioma were analyzed by UALCAN database.Gene Expression Profilling Interactive Analysis(GEPIA)database was used to analyze the correlation between HAX1 and VEGFA.The expression levels of HAX1 and VEGFA mRNA in 30 cases of human glioma and 12 cases of normal brain tissues in the Department of Pathology,Affiliated Hospital of Nantong University were detected by qRT-PCR.Tissue microarray combined with immunohistochemistry(IHC)was used to detect the expression levels of HAX1 and VEGFA proteins in paraffin specimens of 214 glioma patients and 86 normal brain tissues.Then the correlation between HAX1 and VEGFA and the relationships with pathological features and prognosis were further analyzed.GEPIA database was further used to analyze the associations of HAX1 and VEGFA with the survival of the patients.Results Online database analysis showed that both HAX1 and VEGFA mRNA were highly expressed in glioblastoma multiforme(GBM)(P=3.874100E-02,P=1.62436730732907E-12),and they were positively correlated in glioma(r=0.14,P=0.00039).qRT-PCR showed that both HAX1(1.66±0.40)and VEGFA(2.75±0.73)mRNAs were highly expressed in glioma tissues(t=4.744,P<0.0001,t=8.263,P<0.0001).The results from IHC revealed that HAX1(67.8%,145/214)and VEGFA(72.0%,154/214)proteins were more positively expressed in glioma tissues compared to normal brain tissues(χ^(2)=29.174,P<0.05,χ^(2)=33.477,P<0.05),and both were significantly positively correlated(r=0.593,P<0.05).Both HAX1 and VEGFA protein expressions were correlated with Karnofsky Performance Status(KPS),differentiation degree,WHO grading,p53 and Ki-67 protein expression(P<0.05).Survival analysis showed that overall survival(OS)was significantly lower in HAX1-positive

关 键 词：胶质瘤 HAX1 VEGFA 临床病理特征 预后 

分 类 号：R739.41[医药卫生—肿瘤]