CD24基因在人恶性胸膜间皮瘤中的表达及其与预后的关系  

Expression of CD24 gene in human malignant pleural mesothelioma and its relationship with prognosis

作　　者：李彬 周崇熙 普元倩 邱璐[3] 梅雯 熊伟 Li Bin;Zhou Chongxi;Pu Yuanqian;Qiu Lu;Mei Wen;Xiong Wei(College of Basic Medical Sciences,Dali University,Dali 671000,China;Key Laboratory of Clinical Biochemical Testing in Yunnan Province Universities,Dali 671000,China;College of Chemistry and Life Sciences,Chuxiong Normal University,Chuxiong 675000,China;Department of Pathology,Chuxiong Yi Autonomous Prefecture First People's Hospital,Chuxiong 675000,China)

机构地区：[1]大理大学基础医学院,大理671000 [2]云南省高校临床生物化学检验重点实验室,大理671000 [3]楚雄师范学院化学与生命科学系,楚雄675000 [4]楚雄彝族自治州第一人民医院病理科,楚雄675000

出　　处：《中华劳动卫生职业病杂志》2023年第3期168-176,共9页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金项目(32160167、82160516);云南省万人计划青年拔尖人才(2019);云南省应用基础研究专项面上项目(202101AT070006);云南省地方本科高校基础研究联合专项青年项目(2022);云南省教育厅科学研究基金项目(2020J0566、2022J0688、2022J0716、2022Y808);云南省大学生创新创业训练计划项目(2021908);大理市科技计划项目资助(2021KBG032)。

摘　　要：目的分析CD24基因在恶性胸膜间皮瘤(MPM)组织和细胞中的表达水平,探讨其与MPM患者临床病理特征及预后的关系。方法于2021年2月,利用UALCAN数据库分析下载的87例MPM患者CD24基因表达量与临床病理特征的关系。利用TIMER 2.0平台探讨MPM中CD24表达与肿瘤免疫浸润性细胞的关系,利用cBioportal在线工具分析CD24基因与MPM肿瘤标志物基因表达的相关性。采用RT-qPCR分析人正常胸膜间皮细胞系LP9和MPM细胞系NCI-H28(上皮型)、NCI-H2052(肉瘤型)、NCI-H2452(双相混合型),以及18例患者MPM组织及配对的非肿瘤胸膜组织中CD24基因表达量;采用免疫组化分析非肿瘤胸膜组织与MPM组织中CD24蛋白的表达差异。构建Kaplan-Meier模型探讨CD24基因表达量对MPM患者预后的影响,Cox回归分析MPM患者的预后影响因素。结果无TP53突变MPM患者CD24基因表达量明显高于TP53突变MPM患者(P<0.05)。MPM组织中CD24基因表达水平与B细胞呈正相关(r_(s)=0.37,P<0.001)。CD24基因表达与血小板反应蛋白2(THBS2)的表达呈正相关(r_(s)=0.26,P<0.05),与表皮生长因子含腓骨样胞外基质蛋白1(EFEMP1)、间皮素(MSLN)和钙结合蛋白2(CALB2)的表达呈负相关(r_(s)=-0.31、-0.52、-0.43,P<0.05)。RT-qPCR检测发现,MPM细胞(NCI-H28、NCI-H2052和NCI-H2452)中CD24基因表达水平均明显高于正常胸膜间皮LP9细胞,MPM组织中CD24基因表达水平明显高于配对的非肿瘤胸膜组织(P<0.05)。免疫组化结果显示,上皮型和肉瘤型MPM组织CD24蛋白表达量高于配对的非肿瘤胸膜组织。与CD24基因低表达比较,CD24基因高表达MPM患者总体生存率(HR=2.100,95%CI:1.336~3.424)和无疾病进展生存率(HR=1.800,95%CI:1.026~2.625)降低(P<0.05)。Cox多因素分析显示,与双相混合型比较,上皮型是MPM患者预后的保护因素(HR=0.321,95%CI:0.172~0.623,P<0.001);与CD24基因低表达比较,CD24基因高表达是MPM患者预后的独立危险因素(HR=2.412,95%CI:1.291~4.492,P=0.0Objective To investigate the expression of CD24 gene in human malignant pleural mesothelioma(MPM)cells and tissues,and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients.Methods In February 2021,UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients.The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells.cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression.RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28(epithelial type),NCI-H2052(sarcoma type),and NCI-H2452(biphasic mixed type).RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues.The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry.A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients,and Cox regression analysis of prognostic factors in MPM patients was performed.Results The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation(P<0.05).The expression of CD24 gene in MPM was positively correlated with B cells(r_(s)=0.37,P<0.001).The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2(THBS2)(r_(s)=0.26,P<0.05),and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1(EFEMP1),mesothelin(MSLN)and calbindin 2(CALB2)(r_(s)=-0.31,-0.52,-0.43,P<0.05).RT-qPCR showed that the expression level of CD24 gene in MPM cells(NCI-H28,NCI-H2052 and NCI-H2452)was significantly higher than that in normal pleural mesothelial LP9 cells.The expr

关 键 词：间皮瘤 胸膜肿瘤 CD24 RT-QPCR 免疫组织化学 预后 

分 类 号：R734.3[医药卫生—肿瘤]