DNAJB4与非小细胞肺癌免疫细胞浸润和患者预后的相关性分析  

Expression of DNAJB4 and association with immune infiltration and prognosis in non-small cell lung cancer

作　　者：杨上英 黄明翔[1,4] 许德新 刘加夫[3,4] 陈新富 YANG Shangying;HUANG Mingxiang;XU Dexin;LIU Jiafu;CHEN Xinfu(Department of Clinical Laboratory,Fujian Pulmonary Hospital,Fuzhou 350008;Department of Chest Surgery,Fujian Pulmonary Hospital,Fuzhou 350008;Department of Pathology,Fujian Pulmonary Hospital,Fuzhou 350008;Department of Clinical Laboratory,Clinical Teaching Hospital of Fujian Medical University,Fuzhou 350008,Fujian,China)

机构地区：[1]福建省福州肺科医院检验科,福建福州350008 [2]福建省福州肺科医院胸外科,福建福州350008 [3]福建省福州肺科医院病理科,福建福州350008 [4]福建医科大学临床教学医院检验科,福建福州350008

出　　处：《癌变．畸变．突变》2023年第6期467-472,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：福建省福州市科技计划项目(2016-S-129)。

摘　　要：目的:探讨DNAJB4在非小细胞肺癌(NSCLC)中的表达,分析其与癌组织中免疫细胞浸润水平和NSCLC患者预后的相关性。方法:采用GEPIA数据库分析NSCLC患者癌组织和癌旁正常组织中DNAJB4 mRNA的表达差异。采用荧光定量PCR和免疫组+织化学方法检测组织中DNAJB4 mRNA和蛋白的表达。应用TIMER数据库分析DNAJB4表达与NSCLC中免疫细胞(B细胞、CD4 T+细胞、CD8 T细胞、中性粒细胞、巨噬细胞、树突状细胞)浸润水平的相关性,并探讨免疫细胞浸润对NSCLC患者预后的影响。通过Kaplan-Meier plotter数据库分析DNAJB4表达水平与NSCLC预后的关系。结果:与癌旁正常组织比较,DNAJB4在NSCLC组织中低表达(P<0.05)。DNAJB4表达水平与癌组织免疫细胞的浸润程度相关。肺腺癌中,DNAJB4的拷贝数变异对免疫细胞的浸润+水平有明显影响(P<0.05)。B细胞可作为肺腺癌预后的独立危险因素。肺鳞癌中,DNAJB4拷贝数变异对除CD8 T细胞外的免疫细胞浸润水平有显著影响(P<0.05)。生存分析显示低表达的DNAJB4与NSCLC患者的不良预后显著相关(P<0.05)。结论:DNAJB4在NSCLC组织中表达下调,参与NSCLC免疫细胞浸润,影响免疫微环境的平衡,进而造成NSCLC患者的不良预后。DNAJB4可能是NSCLC免疫细胞浸润及预后的生物学标志物。OBJECTIVE:To investigate expression of DNAJB4 in non-small cell lung cancer(NSCLC)and its association with immune cell infiltration levels and prognosis.METHODS:Differences in expression of DNAJB4 mRNA in cancer tissues of NSCLC patients and normal tissues adjacent to the cancers were evaluated based on GEPIA database analysis.Real-time quantitative PCR and immunohistochemical methods were used to detect expressions of DNAJB4 mRNA and protein in NSCLC tissues.The TIMER database was used to analyze correlations between the expression of DNAJB4 and the level of immune cells(B cells,CD4+T cells,CD8+T cells,neutrophils,macrophages,dendritic cells)infiltration in NSCLC,and to explore the prognosis of NSCLC patients with immune cell infiltration.Relationships between expression levels of DNAJB4 and prognosis of NSCLC were evaluated using the Kaplan Meier plot database.RESULTS:Expression of DNAJB4 in NSCLC tissues was lower than that of normal tissues.The low expression was associated with the infiltration levels of immune cells.In lung adenocarcinoma,copy number variations of DNAJB4 had a significant impact on the infiltration levels of immune cells(P<0.05).In addition,B cells served as independent prognostic factors for LUAD.In lung squamous cell carcinoma(LUSC),DNAJB4 copy number variations had a significant impact on immune cell infiltration levels except for CD8+T cells(P<0.05).Survival analysis showed a significant correlation between low expression of DNAJB4 and poor prognosis in NSCLC patients(P<0.05).CONCLUSION:DNAJB4 expression in NSCLC tissues was downregulated,involved in immune cell infiltration into cancer tissues,impacted on the balance of immune microenvironment,and adversely affected prognosis of the patients.DNAJB4 may be useful as a biological marker for immune cell infiltration and prognosis in NSCLC.

关 键 词：DnaJ热休克蛋白家族成员B4 非小细胞肺癌 免疫浸润 预后 

分 类 号：R730.2[医药卫生—肿瘤]