摘要
目的探讨赖氨酰氧化酶(lysyl oxidase,LOX)基因在恶性胸膜间皮瘤(malignant pleural mesothelioma,MPM)细胞和组织中的表达及预后意义。方法采用RT-qPCR和Western blot法分析人胸膜间皮细胞系MeT-5A和MPM细胞系NCI-H28、NCI-H2052、NCI-H2452中LOX mRNA和蛋白表达水平;采用RT-qPCR检测9例MPM组织及配对正常胸膜组织中LOX基因mRNA表达量;通过Oncomine数据库对非肿瘤组织与MPM组织中LOX基因的表达差异进行分析;通过R 3.6.3对TCGA数据库中LOX mRNA表达量与MPM临床病理特征的相关性进行分析;采用基因表达谱动态分析(GEPIA)构建Kaplan-Meier模型探究LOX mRNA表达量对MPM患者预后的影响,并分别对LOX基因与MPM肿瘤标志物基因和赖氨酰氧化酶样蛋白1~4(LOXL1~4)基因表达的相关性进行分析。结果与MeT-5A细胞相比,3种人MPM细胞中LOX mRNA和蛋白的表达水平均提高(P<0.05)。RT-qPCR检测发现,与正常胸膜组织相比,MPM组织中LOX mRNA的表达量增加(P<0.05)。LOX基因表达量与MPM患者T分期相关(P<0.05)。LOX基因高表达者的总生存率和无瘤生存率均低于LOX基因低表达者(P<0.05)。MPM肿瘤标志物间皮素(MSLN)、钙结合蛋白2(CALB2)基因与LOX基因表达呈负相关(P<0.05),而血小板反应蛋白2(THBS2)基因与LOX基因的表达呈正相关(P<0.05)。LOXL2和LOXL4基因与LOX基因表达呈正相关(P<0.05)。结论LOX基因在MPM细胞和组织中高表达,LOX基因高表达提示MPM患者预后不良。
Purpose This study aimed to investigate the expression of lysyl oxidase(LOX)gene in malignant pleural mesothelioma(MPM)cells and tissues and its prognostic significance.Methods RT-qPCR and Western blot were used to analyze the expression levels of LOX mRNA and protein in human pleural mesothelial cell line MeT-5A and three MPM cell lines NCI-H28,NCI-H2052 and NCI-H2452.The mRNA expression of LOX in nine pairs of MPM tissues and matched normal pleural tissues was detected by RT-qPCR.The different expression of LOX gene in non-tumor tissues and MPM tissues was analyzed through the Oncomine database.The correlation between LOX gene mRNA expression and clinicopathological parameters of MPM patients in the TCGA database was analyzed through R 3.6.3.Kaplan-Meier method and log-rank test were used to explore the effect of LOX mRNA expression on the prognosis of MPM patients through gene expression profiling interactive analysis(GEPIA).The correlation analysis of gene expression between LOX and MPM biomarker genes and lysyl oxidase-like 1-4(LOXL1-4)genes were visualized,respectively.Results Compared with MeT-5A cells,the expression levels of LOX mRNA and protein in the three human MPM cells were increased(P<0.05).RT-qPCR detection revealed that compared with normal pleural tissues,the mRNA expression of LOX gene in MPM tissues increased(P<0.05).The expression of LOX gene was correlated with T stage of MPM patients(P<0.05).The overall survival(OS)and disease-free survival(DFS)ofMPM patients with high LOX gene expression were poorer than those with low LOX gene expression(Log-rank P<0.05).The expression of MPM tumor markers mesothelin(MSLN)and calcium binding protein 2(CALB2)genes was significantly negatively correlated with LOX gene expression(P<0.05),while thrombospondin 2(THBS2)gene expression was significantly positively correlated with LOX gene expression(P<0.05).The expression of LOXL2 and LOXL4 genes was significantly positively correlated with LOX gene expression(P<0.05).Conclusion The LOX gene is highly expressed
作者
自加吉
李彬
杨娜
普元倩
李素芬
王唯斯
张态
熊伟
ZI Jia-ji;LI Bin;YANG Na;PU Yuan-qian;LI Su-fen;WANG Wei-si;ZHANG Tai;XIONG Wei(Department of Pathology,College of Basic Medical Sciences,Dali University,Dali 671000,China;Department of Biochemistry and Molecular Biology,College of Basic Medical Sciences,Dali University,Dali 671000,China;Laboratory of Clinical Biochemistry of Yunnan Province,College of Basic Medical Sciences,Dali University,Dali 671000,China)
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2021年第6期699-706,共8页
Chinese Journal of Clinical and Experimental Pathology
基金
云南省教育厅科研基金项目(2020Y0542、2020J0566)
云南省高校病理学与病理生理学硕士研究生导师团队项目(2019)。
关键词
恶性胸膜间皮瘤
LOX
数据挖掘
预后意义
malignant pleural mesothelioma
LOX
data mining
prognostic significance
