中国肺癌杂志2025，Vol.28Issue(3)：183-194,12.DOI:10.3779/j.issn.1009-3419.2025.102.09
NSCLC中TRAF家族蛋白的表达和预后以及功能综合分析
Comprehensive Analysis of the Expression,Prognosis and Function of TRAF Family Proteins in NSCLC
摘要
Abstract
Background and objective Currently,lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world.However,the exact mechanisms underlying lung cancer progression remain unclear.The tumor necrosis factor receptor associated factor(TRAF)family members are cytoplasmic adaptor proteins,which function as both adap-tor proteins and ubiquitin ligases to regulate diverse receptor signalings,leading to the activation of nuclear factor kappa-B(NF-κB),mitogen-activated protein kinase(MAPK)and interferon regulatory factor(IRF)signaling.The aim of this study was to investi-gate the expression of TRAFs in different tissues and cancer types,as well as its mRNA expression,protein expression,prognostic significance and functional enrichment analysis in non-small cell lung cancer(NSCLC),in order to provide new strategies for the diagnosis and treatment of NSCLC.Methods RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues.RNA sequencing data from the Can-cer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines.RNA sequencing data from the The Cancer Genome Atlas(TCGA)database was used to analyze the mRNA lev-els of TRAF family members across different types of human cancers.Immunohistochemistry(IHC)analyses from HPA database were used to analyze the TRAF protein levels in NSCLC[lung adenocarcinoma(LUAD)and lung squamous carcinoma(LUSC)].Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC.The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database.Results The TRAF family members exhibited significant tissue-specific expression heterogeneity.TRAF2,TRAF3,TRAF6 and TRAF7 were widely expressed in most tissues,while the expressions of TRAF1,TRAF4 and TRAF5 were restricted to specific tissues.The expressions of TRAF family members were highly specific among different types of cancer cell lines.In mRNA database of LUAD and LUSC,the expressions of TRAF2,TRAF4,TRAF5 and TRAF7 were significantly upregulated;while TRAF6 did the opposite;move-over,TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC,respectively.Except for TRAF3,TRAF4 and TRAF7,other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with nor-mal tissues.Additionally,patients with higher expression levels of TRAF2,TRAF4 and TRAF7 had shorter overall survival;while patients with higher expression levels of TRAF3,TRAF5 and TRAF6 had significantly longer overall survival;however,no sig-nificant difference had been observed between TRAF1 expression and the overall survival.TRAF family members differentially regulated multiple pathways,including NF-κB,immune response,cell adhesion and RNA splicing.The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvi-ronment,with varying positive and negative correlations among different members.Conclusion TRAF family members exhibit highly specific expression differences across different tissues and cancer types.Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC,whereas,only upregulated expressions of TRAF2,TRAF4 and TRAF7 predict worse prog-nosis.The TRAF family members regulate processes such as inflammation,immunity,adhesion and splicing,and influence the tumor immune microenvironment.关键词
肺肿瘤/肿瘤坏死因子/肿瘤坏死因子受体相关因子/预后/功能Key words
Lung neoplasms/Tumor necrosis factor/Tumor necrosis factor receptor associated factor/Prognosis/Function引用本文复制引用
王逸璇,陈嫱,范亚光,涂姝祺,张洋,张修闻,潘红丽,周雪霞,李雪冰..NSCLC中TRAF家族蛋白的表达和预后以及功能综合分析[J].中国肺癌杂志,2025,28(3):183-194,12.基金项目
本研究受国家自然科学基金项目(No.82273019、No.82172901、No.82472643)、天津市自然科学基金项目(No.22JCYBJC00280、No.22JCYBJC00290)、天津医科大学总医院优秀青年基金项目(No.22ZYYYQ01)、天津市科技重大专项与工程公共卫生科技重大专项重点项目(No.24ZXGZSY00040)和天津市卫生健康科技基金青年项目(No.TJWJ2023QN063)资助 This study was supported by the grants from National Natural Science Foundation of China(No.82273019,to Xuebing LI （No.82273019、No.82172901、No.82472643）
No.82172901,No.82472643,to Xuexia ZHOU),Tianjin Natural Science Foundation(No.22JCYBJC00280,to Xuebing LI （）
No.22JCYBJC00290,to Yaguang FAN),Outstanding Youth Foundation of Tianjin Medical University General Hospital(No.22ZYYYQ01,to Xuexia ZHOU),Tianjin Science and Technology Major Special Project and Engineering-Public Health Sci-ence and Technology Major Special Project Key Project(No.24ZXGZSY00040,to Yaguang FAN),and Tianjin Health Science and Technology Project(No.TJWJ2023QN063,to Qiang CHEN). （No.22ZYYYQ01,to Xuexia ZHOU）
