FADD基因在头颈鳞状细胞癌的预后价值

Prognostic value of FADD gene in head and neck squamous cell carcinoma

目的FADD基因是程序性死亡进程中关键基因,在自噬相关基因模型和HPV阳性多生物标志物的联合研究中,FADD在HNSCC研究中的预后价值已经被研究,但其单个基因在HNSCC预后评估中的研究仍需要进一步深入。本项研究旨在研究FADD基因在头颈鳞状细胞癌的预后价值。方法本研究应用GTEx数据库和TCGA数据库中头颈鳞状细胞癌的表达谱文件,提取FADD基因表达水平。根据FADD基因的高、低分组绘制头颈鳞状细胞癌的Kaplan-Meier曲线,单因素COX分析评价FADD基因的高、低分组对头颈鳞状细胞癌总生存期(Overall Survival,OS)、疾病特异性生存期(Disease Specific Survival,DSS)、无进展生存期(Progress Free Survival,PFS)。再应用斯皮尔曼相关分析方法,对FADD基因及该基因突变与头颈鳞状细胞癌的肿瘤突变负荷、微卫星不稳定性的相关性进行分析。其后应用TCGA portal数据库对头颈部鳞状细胞癌样本数据中FADD基因、年龄、性别、种族、临床分期、肿瘤纯度,与患者的总生存期进行多因素COX分析,进一步分析FADD基因与头颈鳞状细胞癌临床病理参数、免疫细胞之间的关系及FADD基因在头颈鳞状细胞癌中的预后价值。结果FADD基因在头颈鳞状细胞癌组织中表达水平显著高于癌旁正常组织(P<0.05)。FADD基因高、低风险组对头颈鳞状细胞癌的OS、DSS、PFS均都具有显著影响(P<0.05)。FADD基因突变对头颈鳞状细胞癌的微卫星不稳定具有显著影响(P<0.05),并呈正性相关。FADD基因突变对头颈部鳞状细胞癌的肿瘤突变负荷无显著影响(P>0.05)。研究发现头颈部鳞状细胞癌中FADD基因、年龄、肿瘤4期(stageⅣ)是危险因素(P<0.05)。FADD基因水平与头颈鳞状细胞癌中肿瘤免疫浸润细胞静息CD4 T细胞、M0巨噬细胞、中性粒细胞浸润、树突状细胞呈正相关(P<0.05),而与CD8 T细胞、B细胞呈负相关(P<0.05)。结论FADD基因可作为头颈鳞状细胞癌的预后标志物。

Objective FADD gene is a crucial gene in the process of programmed cell death.While its prognostic value in head and neck squamous cell carcinoma(HNSCC)research has been investigated in combination with autophagy-related gene models and HPV-positive multiple biomarkers,further in-depth study of this individual gene in the prognostic assessment of HNSCC is needed.This study aimed to examine the prognostic value of FADD gene in HNSCC.Methods The expression profiles of the FADD gene in HNSCC were extracted from the GTEx and TCGA databases.Kaplan-Meier curves were generated based on high and low expression groups of the FADD gene,and univariate COX analysis was performed to evaluate the impact of these groups on overall survival(OS),diseasespecific survival(DSS),and progression-free survival(PFS)in HNSCC.Furthermore,Spearman correlation analysis was conducted to investigate the correlation of FADD gene and its mutation with tumor mutation burden and microsatellite instability in HNSCC.Subsequently,using the TCGA portal database,a multivariate COX analysis was carried out to assess the association between FADD gene expression,along with age,gender,race,clinical stage,tumor purity,and overall survival in HNSCC sample data.This analysis aimed to further explore the relationship between FADD gene and clinical pathological parameters,as well as the relationship between FADD gene and immune cells,elucidating the prognostic value of FADD gene in HNSCC.Results The expression level of FADD gene in HNSCC tissues was significantly higher compared to adjacent normal tissues(P<0.05).Both high-risk and low-risk groups classified based on FADD gene expression exerted a significant impact on the OS,DSS,and PFS in HNSCC(P<0.05).FADD gene mutation significantly influenced microsatellite instability in HNSCC(P<0.05),exhibiting a positive correlation.FADD gene mutations did not demonstrate a significant effect on tumor mutation burden in HNSCC(P>0.05).Our research revealed that FADD gene,along with age and stage IV tumor,were identified as risk factors in HNSCC(P<0.05).The expression level of FADD gene exhibited positive correlations with the infiltration of tumor immune cells such as resting CD4 T cells,M0 macrophages,neutrophils,and dendritic cells in HNSCC(P<0.05),while showing a negative correlation with CD8 T cells and B cells(P<0.05).Conclusion FADD gene represents a potential prognostic marker for HNSCC.