NUF2基因表达与肺腺癌免疫浸润及临床预后的相关性分析

Correlation analysis of NUF2 gene expression and immune infiltration and clinical prognosis of lung adenocarcinoma

目的:研究NUF2与肺腺癌(lung adenocarcinoma, LUAD)免疫细胞浸润及预后的关系。方法:采用Oncomine数据库分析NUF2在LUAD和肺鳞癌(lung squamous cell carcinoma, LUSC)组织中的表达水平;用GEPIA和PrognoScan数据库评估NUF2对LUAD和LUSC患者预后的影响;采用TIMER数据库分析LUAD中NUF2表达和免疫细胞浸润水平的相关性;采用LinkedOmics数据库进行NUF2相关差异表达基因的GO功能注释和KEGG通路分析。RT-qPCR和Western Blot检测NUF2在肺腺癌细胞中的表达,并采用集落形成实验研究NUF2对肺腺癌细胞增殖的影响。结果:NUF2在LUAD和LUSC组织中的表达水平显著高于正常组织(P<0.01)。NUF2高表达与LUAD患者的总生存率和无疾病生存率负相关(P<0.05),但与LUSC患者的总生存率无相关性。NUF2表达与LUAD组织中B细胞、CD4^(+)T细胞、巨噬细胞和树突状细胞的浸润水平显著负相关(P<0.01)。NUF2相关基因富集在氧化磷酸化等通路,参与的生物学过程有细胞周期检查点和DNA重组等。NUF2在人肺腺癌细胞中高表达,且敲减NUF2可抑制肺腺癌细胞集落形成(P<0.01)。结论:NUF2高表达与LUAD免疫细胞浸润水平降低和不良预后相关,有望成为LUAD潜在的预后标志物和免疫相关治疗靶点。

OBJECTIVE To explore the correlation between the NUF2 gene and immune cell infiltration and clinical prognosis of lung adenocarcinoma(LUAD).METHODS The Oncomine database was used to analyze the expression level of NUF2 in LUAD and lung squamous cell carcinoma(LUSC).The GEPIA and PrognoScan databases were used to evaluate the correlation between NUF2 and clinical prognosis of LUAD and LUSC.The correlation between NUF2 and immune infiltration was analyzed by the TIMER database.The LinkedOmics database was used to analyze the differentially expressed genes related to NUF2 in LUAD,and GO and KEGG analysis were performed.RT-qPCR and Western Blot were used to measure the expression of NUF2 in lung adenocarcinoma cells, and the colony formation experiment was used to study the effect of NUF2 on the proliferation of lung adenocarcinoma cells.RESULTS The mRNA expression of NUF2 in the LUAD and LUSC tumor tissues was significantly higher than that in the normal tissues(P<0.01).The high expression of NUF2 was correlated with poor overall survival and disease-free survival in LUAD(P<0.05),but not in LUSC.The NUF2 mRNA expression negatively correlated with the infiltration levels of B cells, CD4^(+)T cells, macrophages and dendritic cells in LUAD tissues(P<0.01).GO and KEGG analysis showed that NUF2-related genes were enriched in pathways including oxidative phosphorylation, and the biological processes were involved in cell cycle checkpoints and DNA recombination.NUF2 is highly expressed in human lung adenocarcinoma cells, and knocking down NUF2 inhibits the proliferation of lung adenocarcinoma cells(P<0.01).CONCLUSION The high expression of NUF2 is correlated with the decreased of immune cell infiltration level and the poor prognosis in LUAD,and may become a potential prognostic marker and immune-related therapeutic target.