肺腺癌组织中MCM4的表达及其与预后、免疫微环境的相关性分析  

Expression of MCM4 in Lung Adenocarcinoma and Its Correlation with Prognosis and Immune Microenvironment

作　　者：苗毅[1] 杨淑梅[1] 王晶 武润苗 孙皎琳 吴军芳 MIAO Yi;YANG Shumei;WANG Jing;WU Runmiao;SUN Jiaolin;WU Junfang(Department of Respiratory and Critical Care Medicine,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Clinical Laboratory,Shaanxi Provincial People’s Hospital,Xi’an 710068,China)

机构地区：[1]陕西省人民医院呼吸与危重症医学科,西安710068 [2]陕西省人民医院检验科,西安710068

出　　处：《现代检验医学杂志》2023年第5期115-120,共6页Journal of Modern Laboratory Medicine

基　　金：陕西省重点研发计划项目(NO.2020DLSF01-06):OPN/FOXM1信号通路在慢性阻塞性肺疾病气道重塑中的机制研究及临床价值。

摘　　要：目的 探讨肺腺癌(lung adenocarcinoma,LUAD)组织中微小染色体维持蛋白4(minichromosome maintenance proteins 4, MCM4)的表达及其与预后、免疫微环境的相关性。方法 选取2021年1~7月陕西省人民医院收治的LUAD患者4例,应用转录组测序检测LUAD患者癌组织和癌旁组织MCM4表达水平。癌症基因组图谱肺腺癌(the cancer genome atla-LUAD,TCGA-LUAD)数据用于验证LUAD中MCM4表达并探究其与生存期的相关性。采用LinkedOmics分析LUAD中MCM4共表达基因、功能富集及调控因子靶向富集情况。STRING用于构建蛋白质-蛋白质互作网络。采用TIMER分析MCM4与LUAD肿瘤免疫微环境的相关性。COX回归分析LUAD患者预后的影响因素。结果 与癌旁组织比较,LUAD癌组织中MCM4表达水平(6.50±0.86 vs 4.22±0.66)升高,差异有统计学意义(U=16,P=0.029)。TCGA-LUAD发现相似结果(癌组织3.63±0.92 vs癌旁组织1.90±0.28),差异有统计学意义(U=30 355,P <0.001)。生存分析显示,MCM4高表达LUAD患者总生存期和无病生存期200个月的累积生存率(8.79%和19.25%)均低于MCM4低表达患者(28.87%和36.82%),差异有统计学意义(风险比=1.7,1.4,均P<0.05)。共表达分析显示,LUAD中与MCM4正相关的基因主要参与P53信号通路、DNA复制、错配修复等通路。肿瘤免疫微环境分析显示,MCM4与中性粒细胞浸润呈正相关(partial.cor=0.14,P=0.002),与B细胞浸润呈负相关(partial.cor=-0.152,P<0.001)。COX回归分析显示,MCM4是影响LUAD患者预后的独立因子。结论 LUAD癌组织中MCM4表达升高,与预后及免疫微环境显著相关,可作为LUAD患者不良预后评估的分子标志物。Objective To explore the expression of minichromosome maintenance proteins 4(MCM4)in lung adenocarcinoma(LUAD)and its correlation with prognosis and immune microenvironment.Methods From January to July 2021,four LUAD patients admitted to Shaanxi Provincial People’s Hospital were selected and transcriptome sequencing was used to detect the expression level of MCM4 in LUAD cancer tissue and paracancerous tissue.TCGA-LUAD data was performed to validate the expression of MCM4 and explore its relevance to survival periods in LUAD.Co-expressed genes of MCM4,functional enrichment,and regulator target enrichment in LUAD were analyzed using LinkedOmics.STRING tool was adopted to construct the protein-protein interaction network.TIMER tool was utilized to investigate the relationship between MCM4 and the tumor immune microenvironment in LUAD.COX regression was used to analyze the influencing factors of prognosis for LUAD patients.Results Compared with the paracancerous tissues,the expression level of MCM4 in LUAD cancer tissues was increased(6.50±0.86 vs 4.22±0.66),and the difference was statistically significant(U=16,P=0.029).TCGA-LUAD data found a similar result(cancer tissues 3.63±0.92 vs paracancerous tissues 1.90±0.28),and the difference was statistically significant(U=30355,P<0.001).Survival analysis showed that the 200-month cumulative survival rate of OS and DFS of LUAD patients with high-expression MCM4(8.79%and 19.25%)was lower than that with low-expression MCM4(28.87%and 36.82%),and the differences was statistically significant(HR=1.7,1.4,all P<0.05).Co-expression analysis revealed that the genes that were positively correlated with MCM4 in LUAD,were mainly involved in the P53 signaling pathway,DNA replication,and mismatch repair.Tumor immune microenvironment analysis showed that MCM4 was positively correlated with the infiltration of Neutrophils(partial.cor=0.14,P=0.002),and negatively correlated with the infiltration of B cells(partial.cor=-0.152,P<0.001).COX regression analyses found that MCM4 was a

关 键 词：肺腺癌 微小染色体维持蛋白4 肿瘤免疫微环境 

分 类 号：R734.2[医药卫生—肿瘤] R730.43[医药卫生—临床医学]