核仁蛋白16在肺腺癌中的表达及其临床意义

Expression and clinical significance of NOP16 in lung adenocarcinoma

目的探讨核仁蛋白16(NOP16)在肺腺癌(LUAD)中的表达及其临床意义。方法收集并比较癌症基因组图谱数据库(TCGA)中445例LUAD和54例正常肺组织样本NOP16 mRNA表达水平的差异,收集、验证并比较基因表达综合数据库(GEO)中226例LUAD和20例正常肺组织样本NOP16 mRNA表达水平的差异;采用Wilcoxon秩和检验和Kruskal-WallisH检验比较不同临床病理特征的LUAD患者NOP16 mRNA表达水平的差异;通过Kaplan-Meier法评估NOP16在LUAD中的预后价值;采用基因集富集分析(GSEA)探讨NOP16在LUAD中可能参与的生物学通路;通过肿瘤免疫评估资源(TIMER)数据库评估NOP16 mRNA表达水平与肿瘤浸润性免疫细胞(TIICs)的关系。结果在LUAD中NOP16 mRNA表达水平明显高于正常肺组织(P<0.01),且不同临床分期、T分期、N分期的LUAD患者NOP16 mRNA表达水平均差异有统计学意义(均P<0.05)。Kaplan-Meier生存分析表明NOP16 mRNA的高表达与LUAD患者的不良预后相关(P<0.05)。GSEA显示在NOP16高表达组,核糖体、DNA复制、错配修复、p53信号通路被显著富集(P<0.05,FDR<0.25)。在LUAD中,NOP16 mRNA表达水平与B细胞(r=-0.22)、CD4^(+)T细胞(r=-0.25)、CD8^(+)T细胞(r=-0.12)、中性粒细胞(r=-0.18)、巨噬细胞(r=-0.27)和树突状细胞(r=-0.25)的浸润丰度均呈负相关(均P<0.01)。结论NOP16有望成为LUAD诊断和预后评估的生物标志物以及免疫治疗的新靶点。

ObjectiveTo investigate the expression and clinical significance of nucleolar protein 16(NOP16)in lung adenocarcinoma(LUAD).MethodsThe NOP16 mRNA expression level differential was gathered and confirmed between 445 LUAD samples and 54 normal lung samples from the Cancer Genome Atlas(TCGA),and 226 LUAD samples and 20 normal lung samples from the Gene Expression Omnibus(GEO).The mRNA expression of NOP16 was compared in LUAD patients with various clinicopathological characteristics using the Wilcoxon rank-sum test and the Kruskal-WallisHtest.The Kaplan-Meier method was used to assess NOP16′s prognostic value in LUAD.The putative biological pathway of NOP16 in LUAD was investigated using Gene Set Enrichment Analysis(GSEA).Using the Tumor Immune Assessment Resource(TIMER)database,researchers examined the relationship between NOP16 mRNA expression and tumor-infiltrating immune cells(TIICs).ResultsNOP16 mRNA expression in LUAD was significantly higher than that in normal lung tissue(P<0.01),and the NOP16 mRNA expression levels differed statistically among different clinical stages,T stages and N stages(allP<0.05).According to a Kaplan-Meier survival analysis,increased NOP16 mRNA expression was associated with a poor prognosis in LUAD patients(P<0.05).The ribosome,DNA replication,mismatch repair,and p53 signaling pathways were highly enriched in the NOP16 mRNA high expression group(P<0.05,FDR<0.25).NOP16 expression was inversely related to the abundance of B cells(r=-0.221),CD4^(+)T cells(r=-0.254),CD8^(+)T cells(r=-0.12),neutrophils(r=-0.184),macrophages(r=-0.274),and dendritic cells(r=-0.246)(allP<0.01).ConclusionNOP16 is likely to become a biomarker for LUAD diagnosis and prognosis,as well as a new therapeutic target.