【摘要】 目的 探究早期生长反应因子1(early growth response gene 1,EGR1)在非小细胞肺癌(non-small cell lung cancer, NSCLC)中的表达特征，及其与免疫细胞浸润、程序性死亡配体1(programmed death factor ligand 1,PD-L1)表达的关联。方法 基于癌症基因组图谱(the cancer genome atlas, TCGA)和基因表达综合(gene expression omnibus, GEO)数据库分析EGR1在NSCLC癌中的表达差异；利用TNMplot数据库分析EGR1与NSCLC临床特征的相关性，采用Kaplan-Meier Plotter数据库分析EGR1与患者预后的关系；通过细胞×基因数据库和TIMER数据库分析EGR1表达与免疫细胞浸润的相关性，并验证其与PD-L1的表达关联；最后通过免疫组化SP法进行实验验证。结果 EGR1在多种肿瘤组织中表达异常，在肺肿瘤组织中显著低于正常组织，其表达与NSCLC的肿瘤分期显著相关(P<0.05),与转移无关。NSCLC中EGR1低表达患者的总生存期(overall survival, OS)、进展后生存期(post-progression survival, PPS)和无进展生存期(progression-free survival, PFS)均显著缩短(P<0.01)。EGR1与B细胞、CD8~+ T细胞、CD4~+ T细胞、巨噬细胞等呈显著正相关(P<0.05)。EGR1与PD-L1表达存在正相关(P<0.01)。免疫组化结果显示PD-L1低表达组中EGR1表达显著降低(P=0.001 7)。结论 本研究揭示了EGR1在NSCLC中通过调控肿瘤免疫而影响肿瘤预后的新机制，同时明确EGR1与PD-L1的相关性为肿瘤免疫治疗预后评估体系的完善及治疗策略的优化提供了新的思路。更多还原

【Abstract】 Objective To investigate the expression characteristics of early growth response factor 1(EGR1) in non-small cell lung cancer(NSCLC) and its correlation with immune cell infiltration and PD-L1 expression.Methods The expression differences of EGR1 in NSCLC were analyzed based on the cancer genome atlas(TCGA) and gene expression omnibus(GEO) databases.The TNMplot database was used to analyze the association between EGR1 and clinical features of NSCLC, and the Kaplan-Meier Plotter database was applied to explore the correlation between EGR1 and lung cancer prognosis. The correlations between EGR1 expression and immune cell infiltration, as well as the association between EGR1 and PD-L1 expression, were analyzed with CELL×GENE and TIMER databases, and verified by immunohistochemical(SP) staining.Results EGR1 was abnormally expressed in multiple tumors, and its expression in lung tumor tissues was significantly lower than that in normal tissues. EGR1 expression was significantly associated with tumor staging of NSCLC, but not with tumor metastasis. The overall survival(OS), post-progression survival(PPS), and progression-free survival(PFS) of NSCLC patients with low EGR1 expression were significantly shortened. EGR1 expression was positively correlated with infiltration of B cells, CD8~+ T cells, CD4~+ T cells, and macrophages, etc(P<0.05). A positive correlation was found between EGR1 and PD-L1 expression(P<0.01). Immunohistochemistry showed that EGR1 expression was significantly lower in the PD-L1 low-expression group(P=0.001 7).Conclusion In NSCLC, low EGR1 expression may lead to poor prognosis by affecting immune cells, and analyzing the correlation between EGR1 and PD-L1 can provide guidance for prognosis evaluation and immunotherapy of NSCLC.更多还原