PSMA4在肺腺癌预后、诊断和免疫浸润中的作用和机制研究  

Role and mechanism of PSMA4 in prognosis,diagnosis and immune infiltration of lung adenocarcinoma

作　　者：赵静 李艳梅 王雪樾 聂恬 王洁 翁启明 张静 范晔 ZHAO Jing;LI Yanmei;WANG Xueyue;NIE Tian;WANG Jie;WENG Qiming;ZHANG Jing;FAN Ye(Training Center for Clinical Skills,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037;Department of Clinical Laboratory,General Hospital of Western Theater Command,Chengdu,Sichuan Province,610083;Department of Pediatrics,General Hospital of Xizang Command,Lasha,Xizang Autonomous Region,850000;Digestive Endoscopy Center,Sichuan Provincial People’s Hospital,Chengdu,Sichuan Province,610072,China;Institute of Field Internal Medicine,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037;Department of Respiratory Diseases,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037)

机构地区：[1]陆军军医大学(第三军医大学)第二附属医院临床技能培训中心,重庆400037 [2]中国人民解放军西部战区总医院检验科,成都610083 [3]中国人民解放军西藏军区总医院儿科,拉萨850000 [4]四川省人民医院消化内镜中心,成都610072 [5]陆军军医大学(第三军医大学)第二附属医院野战内科研究所,重庆400037 [6]陆军军医大学(第三军医大学)第二附属医院呼吸科,重庆400037

出　　处：《陆军军医大学学报》2024年第17期1985-1993,共9页Journal of Army Medical University

基　　金：重庆市科卫联合项目(2023QNXM010)。

摘　　要：目的探究PSMA4在肺腺癌(lung adenocarcinoma,LUAD)预后、诊断和免疫浸润中的作用和机制。方法从癌症基因组图谱(the cancer genome atlas,TCGA)数据库中获取LUAD患者的表达谱和临床信息。通过Wilcoxon秩和检验比较LUAD组(n=539)与正常组(n=59)PSMA4基因的表达水平。通过在GEO数据库下载GSE40791和GSE10072 LUAD数据集,验证PSMA4在LUAD组与正常组中的表达水平。收集10对2023年1-12月在陆军军医大学第二附属医院呼吸科进行纤维支气管镜肺活检术的LUAD患者的肿瘤和癌旁组织样本。采用RT-qPCR技术验证PSMA4在10对LUAD和癌旁组织中的表达。体外培养肺癌细胞和正常肺上皮细胞,通过RT-qPCR检测PSMA4在各组细胞中的表达。并对PSMA4的高低表达组进行了功能富集分析和免疫细胞浸润分析,通过Cox回归分析和Kaplan-Meier(KM)法确定PSMA4对于LUAD的诊断和预后的价值,并构建列线图预测不同时间点的总生存率。结果TCGA数据集、GSE40791和GSE10072 LUAD数据集中的表达数据显示,PSMA4在LUAD组中的表达明显高于正常组(P<0.01)。RT-qPCR检测分析发现,PSMA4在LUAD和肺癌细胞中的表达显著高于癌旁组织和正常肺上皮细胞(P<0.01)。PSMA4高表达是诊断LUAD和预后不良的标志物,与肿瘤微环境中效应记忆性T细胞、滤泡辅助性T细胞、B淋巴细胞、自然杀伤细胞、中央记忆性T细胞、肥大细胞的水平的降低有关。结论PSMA4对LUAD有良好的诊断效能,并且与LUAD的预后和免疫浸润密切相关。Objective To investigate the role of PSMA4 in the prognosis,diagnosis and immune infiltration of lung adenocarcinoma(LUAD),and explore its underlying mechanism.Methods The expression profiles and clinical data of LUAD patients were sourced from the Cancer Genome Atlas(TCGA)database.The expression level of PSMA4 in LUAD tissues(n=539)and normal tissues(n=59)were compared using the Wilcoxon rank-sum test.The expression levels of PSMA4 in LUAD tissues and normal tissues were validated by analyzing the GSE40791 and GSE10072 LUAD datasets obtained from the Gene Expression Omnibus(GEO)database.In addition,tumor and adjacent non-cancerous tissues were collected from 10 LUAD undergoing lung biopsy by fiberoptic bronchoscopy in Second Affiliated Hospital of Army Medical University from January to December 2023.The PSMA4 expression in above samples was further verified using RT-qPCR.RT-qPCR was performed to detect the expression of PSMA4 in lung cancer cells and normal lung epithelial cells.Functional enrichment analysis and immune cell infiltration analysis were conducted on the cells with high and low expression of PSMA4.Cox regression analysis and Kaplan-Meier(KM)survival analysis were used to determine the diagnostic and prognostic value of PSMA4 for LUAD,and a nomogram was constructed to predict the overall survival rate at different time points.Results The analysis of TCGA datasets,GSE40791,and GSE10072 LUAD data revealed that PSMA4 expression was significantly higher in LUAD tissues than in normal tissues(P<0.01).RT-qPCR further confirmed that the expression of PSMA4 was obviously elevated in LUAD tissues and lung cancer cells than adjacent non-cancerous tissues and normal lung epithelial cells(P<0.01).High PSMA4 expression could be regarded as a marker for LUAD diagnosis and poor prognosis,and was associated with reduced proportions of Tem cells,TFH cells,B cells,NK cells,Tcm cells,and mast cells in the tumor microenvironment.Conclusion PSMA4 presents significant diagnostic performance for LUAD,and is closely assoc

关 键 词：肺腺癌 PSMA4 预后 诊断 免疫浸润 

分 类 号：R394.3[医药卫生—医学遗传学] R730.23[医药卫生—基础医学] R734.2