FOXI3在头颈部鳞状细胞癌中的表达及相关性分析

Expression and Correlation Analysis of FOXI3 in Head and Neck Squamous Cell Carcinoma

目的:探究叉头盒I3基因(FOXI3)在头颈部鳞状细胞癌(HNSC)组织中的表达及其对HNSC患者预后的影响,阐明FOXI3在HNSC发生发展中的作用。方法:从肿瘤基因组图谱(TCGA)下载HNSC的基因表达数据和相应的临床信息。使用TIMER 2.0、GEPIA和UALCAN在线数据库验证FOXI3在HNSC中的表达。应用WilCoxon秩和检验分析FOXI3在非配对样本及配对样本中的表达差异。应用R软件ggplot2包分析TCGA数据集中FOXI3表达与HNSC临床因素之间的相关性。应用Cox回归分析TCGA数据库中具有预后信息的HNSC患者,Kaplan Meier数据库及GEPIA数据库验证上述结果。使用R软件进行单因素和多因素Cox分析。使用GeneMania及STRING数据库对FOXI3相互作用基因和蛋白质进行鉴定,同时应用R软件的clusterProfiler包对相互作用的基因进行富集分析。应用TIMER 2.0分析HNSC中FOXI3表达与癌症相关成纤维细胞的浸润水平的相关性。应用R软件GSVA包的ssGSEA算法估计TCGA数据库中HNSC患者FOXI3表达与免疫浸润之间的相关性。结果:FOXI3在HNSC中的表达显著高于正常组织,差异具有统计学意义(P<0.001)。FOXI3基因表达升高的HNSC患者总体生存率(OS)及疾病特异性生存期(DSS)较低表达组差,差异具有统计学意义(P<0.05)。单因素Cox回归显示FOXI3可作为独立的预后因素。GeneMania数据库及STRING数据库显示,与FOXI3相互关联的基因较多,富集分析显示其参与的细胞组分、分子功能、生物学过程及信号通路较复杂。基于MCPCOUNTER、TIDE、EPIC算法,HNSC的FOXI3表达与癌症相关成纤维细胞的浸润水平呈正相关。在HNSC中FOXI3与NK CD56bright细胞浸润水平呈正相关,而与多种免疫细胞的浸润水平呈负相关。结论:FOXI3在HNSC组织中的表达高于正常组织,且其高表达可能与HNSC的发生、发展及不良预后相关,FOXI3可作为HNSC诊断与预后的候选指标。

Objective To investigate the expression of forkhead box-3 (FOXI3) in the head and neck squamous cell carcinoma(HNSC)tissue and its impact on the prognosis of the HNSC patients,and to clarify the role of FOXI3 in the development and progression of HNSC.Methods Gene expression data and clinical information of HNSC were downloaded from The Cancer Genome Atlas (TCGA).The expression of FOXI3 in HNSC was verified using TIMER 2.0,GEPIA and UALCAN online databases.WilCoxon rank sum test was used to analyze the expression differences of FOXI3 in unpaired samples and paired samples.R software ggplot2 package was used to analyze the correlation between FOXI3 expression and HNSC clinical factors in TCGA data sets.The results were verified by Cox regression analysis of HNSC patients with prognostic information in TCGA,Kaplan Meier and GEPIA databases.R software was used for univariate and multivariate Cox analysis.GeneMania and STRING database were used to identify genes and proteins interacting with FOXI3,and clusterProfiler package of R software was used to enrich and analyze genes interacting with FOXI3.TIMER 2.0 was used to analyze the correlation between the expression of FOXI3 in HNSC and the invasion level of cancer-associated fibroblasts.The ssGSEA algorithm of R software GSVA package was used to estimate the correlation between FOXI3 expression and immune infiltration in HNSC patients in TCGA database.Results The expression of FOXI3 in HNSC tissues was significantly higher than that in normal tissues (P < 0.001).The overall survival (OS) and disease-specific survival (DSS) of HNSC patients with increased FOXI3 gene expression were worse than those of the low-expression group,and the differences were statistically significant (P < 0.05).Univariate Cox regression showed that FOXI3 was an independent prognostic factor.GeneMania database and STRING database showed that there were many genes associated with FOXI3,and enrichment analysis showed that they were involved in complex cellular components,molecular functions,biological processes and signaling pathways.Based on MCPCOUNTER,TIDE and EPIC algorithms,the expression of FOXI3 in HNSC was positively correlated with the invasion level of cancer-related fibroblasts.In HNSC,FOXI3 was positively correlated with NK CD56bright cell infiltration level,but negatively correlated with various immune cells infiltration level.Conclusion The expression of FOXI3 in HNSC tissues is higher than that in the normal tissues,and its high expression may be related to the occurrence,development and poor prognosis of HNSC.FOXI3 can be used as a candidate indicator for the diagnosis and prognosis of HNSC.