GNPNAT1与HDAC11在非小细胞肺癌组织中的表达及其临床意义  

Expression and clinical significance of GNPNAT1 and HDAC11 in non-small cell lung cancer tissues

作　　者：沈洁 张洁 SHEN Jie;ZHANG Jie(Department of Clinical Laboratory,Hai'an People's Hospital,Jiangsu Hai'an 226600,China;Department of Immunology,Nantong University Medical College,Jiangsu Nantong 226019,China)

机构地区：[1]海安市人民医院检验科,江苏海安226600 [2]南通大学医学院免疫学系,江苏南通226019

出　　处：《现代肿瘤医学》2024年第21期4089-4095,共7页Journal of Modern Oncology

基　　金：国家自然科学基金面上项目(编号:31770935);江苏省重点研发计划专项资金项目(编号:BE2020667)。

摘　　要：目的:探讨磷酸氨基葡萄糖-N-乙酰基转移酶1(glucosamine-phosphate N-acetyltransferase 1,GNPNAT1)与组蛋白去乙酰化酶11(histone deacetylases 11,HDAC11)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其临床意义。方法:采用免疫组织化学(immunohistochemistry,IHC)染色检测GNPNAT1和HDAC11蛋白在158例手术切除NSCLC组织及癌旁组织中的表达。分析两者表达与肿瘤病理组织学特征的关系,通过Kaplan-Meier曲线计算不同表达水平组患者的总体生存(overall survival,OS)率。进行单、多因素Cox回归分析确定NSCLC患者的独立预后因素。结果:GNPNAT1(Z=8.611,P<0.001)与HDAC11(Z=7.731,P<0.001)在NSCLC组织中表达显著高于其邻近癌旁组织。根据IHC染色结果,在158例NSCLC样本中观察到GNPNAT1高表达80例(50.6%),HDAC11高表达75例(47.5%)。GNPNAT1高表达在中、低分化(χ^(2)=33.747,P<0.001)及TNMⅡ-Ⅲ期肿瘤(χ^(2)=13.664,P=0.001)中更为常见,淋巴结转移率更高(χ^(2)=10.534,P=0.001),淋巴血管侵犯更为频繁(χ^(2)=5.425,P=0.020)。HDAC11高表达与淋巴结转移(χ^(2)=8.265,P=0.004)、胸膜侵犯(χ^(2)=4.373,P=0.037)及TNM分期(χ^(2)=6.472,P=0.039)显著相关。GNPNAT1高、低表达者3年OS率分别为67.5%和88.3%(χ^(2)=16.362,P<0.001),而HDAC11高、低表达患者3年OS率分别为61.4%和91.3%(χ^(2)=8.864,P=0.003)。单、多变量Cox回归分析显示,GNPNAT1(P=0.014,HR:2.236,95%CI:1.180~4.239)和HDAC11高表达(P=0.042,HR:1.813,95%CI:1.022~3.218)是NSCLC患者的独立预后因素。结论:GNPNAT1和HDAC11高表达与肿瘤侵袭性特征及不良预后有关,两者或许是NSCLC患者的潜在预后标志物。Objective:To investigate the expression of glucosamine-phosphate N-acetyltransferase 1(GNPNAT1)and histone deacetylases 11(HDAC11)and their clinical significance in non-small cell lung cancer(NSCLC).Methods:Immunohistochemistry(IHC)staining was used to detect the expression of GNPNAT1 and HDAC11 proteins in 158 surgically resected NSCLC tissues and adjacent normal tissues.The relationships between the expression of the two proteins and tumor histopathological characteristics were analyzed,and the overall survival(OS)rates of NSCLC patients with high and low expression of GNPNAT1 and HDAC11 were calculated by Kaplan-Meier methods.The univariate and multivariate Cox regression analysis were conducted to determine independent prognostic factors for NSCLC patients.Results:The expression of GNPNAT1(Z=8.611,P<0.001)and HDAC11 protein(Z=7.731,P<0.001)were higher in NSCLC tissues than in adjacent normal tissues.According to the results of IHC staining,high expression of GNPNAT1 protein was observed in 80 cases(50.6%)and high expression of HDAC11 protein was detected in 75 cases(47.5%)of 158 NSCLC samples.The proportions of moderate/poor differentiation(χ^(2)=33.747,P<0.001)and TNM stageⅡ-Ⅲ(χ^(2)=13.664,P=0.001)were higher,and lymph node metastasis(χ^(2)=10.534,P=0.001)and lymphovascular invasion(χ^(2)=5.425,P=0.020)were more frequent in patients with high expression of GNPNAT1.On the other hand,high expression of HDAC11 was significantly correlated with lymph node metastasis(χ^(2)=8.265,P=0.004),perineural invasion(χ^(2)=4.373,P=0.037)and TNM stage(χ^(2)=6.472,P=0.039).The 3-year OS rates of patients with high and low GNPNAT1 expression were 67.5%and 88.3%,respectively(χ^(2)=16.362,P<0.001).The 3-year OS rates of patients with high and low HDAC11 expression were 61.4%and 91.3%,respectively(χ^(2)=8.864,P=0.003).Univariate and multivariate Cox regression analysis demonstrated that high expression of GNPNAT1(P=0.014,HR:2.236,95%CI:1.180~4.239)and HDAC11(P=0.042,HR:1.813,95%CI:1.022~3.218)were independent progno

关 键 词：非小细胞肺癌 磷酸氨基葡萄糖-N-乙酰基转移酶1 组蛋白去乙酰酶11 免疫组化 预后标志物 

分 类 号：R734.2[医药卫生—肿瘤]