中国肺癌杂志2025,Vol.28Issue(4):256-266,11.DOI:10.3779/j.issn.1009-3419.2025.102.12
基于公共数据库探讨DDB1在肺腺癌中的表达和作用
Public Database-based Study to Explore the Expression and Role of DDB1 in Lung Adenocarcinoma
摘要
Abstract
Background and objective Lung adenocarcinoma(LUAD)is the predominant subtype of non-small cell lung cancer(NSCLC).Damage-specific DNA binding protein 1(DDB1),as a core protein of the CUL4-DDB1 ubiquitin ligase complex,is involved in the regulation of DNA damage repair,epigenetic modification,and cell cycle checkpoint activa-tion.While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported,its expression and role in LUAD remain to be elucidated.This study aims to investigate the expression and role of DDB1 in LUAD.Methods The expression,clinicopathological features and prognosis of DDB1 in LUAD were analysed using databases such as UALCAN,Kaplan-Meier Plotter and GEPIA;The interaction network and enriched functional path-ways were constructed by GeneMANIA and Metascape;the correlation between DDB1 and immune cells by combining with TISIDB infiltration was evaluated,and the clustering results of cell subtypes and the expression of DDB1 in different immune cell subpopulations were analysed by single-cell sequencing;finally,tissue microarrays were used to further verify the expres-sion and prognostic value of DDB1 in LUAD.Results The mRNA and protein expression of DDB1 in LUAD tissues were significantly higher than those in normal tissues(P<0.01),and the high expression correlated with later clinical stage(P<0.001),lymph node metastasis(P<0.001)and poor prognosis(P<0.001).Functional enrichment showed that DDB1 was involved in DNA repair and RNA transcriptional regulation,and TISIDB evaluation revealed that DDB1 was negatively correlated with the expression level of immune cells,suggesting the potential regulation of the immune microenvironment.Single cell analysis showed that DDB1 was mainly expressed in T cells,alveolar macrophages and dendritic cells.Tissue microarrays confirmed that overall survival was shorter in the DDB1 high expression group(P<0.001),and Cox multifactorial analysis showed that DDB1 was an independent predictor of LUAD prognosis.Conclusion DDB1 is highly expressed in LUAD,which is associated with poor prognosis,and is closely related to tumor immune cell infiltration,and is involved in tumourigenesis and develop-ment through DNA repair and RNA transcriptional regulation.DDB1 can be used as a potential prognostic marker and thera-peutic target for LUAD.关键词
肺肿瘤/DDB1/预后/生物标志物Key words
Lung neoplasms/DDB1/Prognosis/Biomarker引用本文复制引用
邹昕锴,何子轶,张雁飞,胡奕,王晓敏,吴中杰..基于公共数据库探讨DDB1在肺腺癌中的表达和作用[J].中国肺癌杂志,2025,28(4):256-266,11.基金项目
本研究受2020年嘉兴市公益性研究计划项目(No.2020AD30073)和2020年度浙江省中医药科学研究基金项目(A类)(No.2020ZA114)资助 This study was supported by the grants from 2020 Jiaxing City Public Welfare Research Programme Project(No.2020AD30073)and 2020 Zhejiang Province Traditional Chinese Medicine Scientific Research Fund Project(Class A)(No.2020ZA114)(Both to Zhongjie WU). (No.2020AD30073)