医学新知2024,Vol.34Issue(3) :291-300.DOI:10.12173/j.issn.1004-5511.202306014

MTHFD2与头颈部鳞状细胞癌的肿瘤微环境相关性

The correlation between MTHFD2 and the tumor microenvironment in head and neck squamous cell carcinoma

史振祥 吴洒 蔡伟松 明小平 陈雄
医学新知2024,Vol.34Issue(3) :291-300.DOI:10.12173/j.issn.1004-5511.202306014

MTHFD2与头颈部鳞状细胞癌的肿瘤微环境相关性

The correlation between MTHFD2 and the tumor microenvironment in head and neck squamous cell carcinoma

史振祥 1吴洒 2蔡伟松 1明小平 1陈雄1
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作者信息

  • 1. 武汉大学中南医院耳鼻咽喉头颈外科(武汉 430071)
  • 2. 华中科技大学同济医学院附属湖北妇幼保健院妇科Ⅱ(武汉 430070)
  • 折叠

摘要

目的 采用生物信息学分析技术探讨亚甲基四氢叶酸脱氢酶 2(methylenetetrahydrofolate dehydrogenase 2,MTHFD2)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达、生物学功能、相关信号通路、肿瘤突变负荷、免疫细胞浸润及其与患者预后的关系.方法 在癌症和肿瘤基因图谱(TCGA)数据库中比较人HNSCC组织和正常组织中MTHFD2基因mRNA的相对表达水平,根据HNSCC患者癌组织中MTHFD2基因表达中位数分为高、低表达组,绘制Cox比例风险模型,Log-rank检验比较MTHFD2 高低表达组患者总生存期(OS)有无差异;对MTHFD2及相关基因功能进行KEGG和GO信号通路功能富集;使用R语言与maftools软件包分析MTHFD2与肿瘤突变负荷的相关性;使用TIMER 2.0相关模块分析癌组织肿瘤浸润情况.结果 MTHFD2基因mRNA在癌组织表达水平高于癌旁正常组织(P<0.05),随着MTHFD2基因mRNA表达水平的增高,HNSCC的分期增加(P<0.05),OS缩短(P<0.05);GSEA发现MTHFD2与细胞周期控制过程密切相关;MTHFD2的体细胞突变率为0.59%,且与肿瘤突变负荷显著相关(P<0.001);MTHFD2高表达时,NK CD56 bright细胞、T辅助细胞和Th2细胞显著上升.结论 MTHFD2可能作为HNSCC的预后性生物标志物,并可能在肿瘤浸润免疫细胞中发挥关键作用.

Abstract

Objective To investigate the expression,biological function,related signaling pathways,tumor mutation burden(TMB),immune infiltration and prognosis of methylene tetrahydrofolate dehydrogenase 2(MTHFD2)in head and neck squamous carcinoma(HNSCC)by bioinformatics analysis techniques.Methods The relative expression levels of MTHFD2 gene mRNA in HNSCC tissues and normal tissues were compared in the Cancer Genome Atlas(TCGA)database.According to the median expression of MTHFD2 gene in HNSCC tissues,the patients were divided into high and low expression groups,and the cox proportional-hazards model was drawn.Log-rank test was used to compare the overall survival(OS)of patients with high and low expression of MTHFD2,and the KEGG and GO signaling pathway function enrichment of MTHFD2 and related gene functions was performed.R software with maftools package was used to analyze the correlation between MTHFD2 and TMB,the TIMER 2.0 correlation module was used to evaluate cancer tissue tumor infiltration.Results MTHFD2 mRNA in HNSCC cancer tissues was higher than that in adjacent normal tissues(P<0.05).With the increase of MTHFD2 mRNA expression level,the OS decreased(P<0.05)and the stage of HNSCC increased(P<0.05).GSEA revealed that MTHFD2 is closely associated with cell cycle control processes.MTHFD2 presented 0.59%somatic mutation rate and significant correlation with tumor mutation burden(P<0.001).Tumor infiltrating immune cells analysis revealed that the proportional of NK CD56 bright cell,Th2 cells and T helper cells changed significantly when MTHFD2 expression was high.Conclusion MTHFD2 could be identified as a promising prognostic biomarker,and probably plays a crucial role in immune cell infiltration in HNSCC.

关键词

MTHFD2/头颈部鳞状细胞癌/预后/肿瘤突变负荷

Key words

MTHFD2/Head and neck squamous cell carcinoma/Prognosis/Tumor mutation burden

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基金项目

中南医院科技创新培育基金面上培育项目(CXPY2020046)

出版年

2024
医学新知
武汉大学中南医院,中国农工民主党湖北省委医药卫生工作委员会

医学新知

CSTPCD
影响因子:0.243
ISSN:1004-5511
参考文献量32
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