Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma

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...

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Main Authors: Xinkai ZOU, Ziyi HE, Yanfei ZHANG, Yi HU, Xiaomin WANG, Zhongjie WU
Format: Article
Language:zho
Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2025-04-01
Series:Chinese Journal of Lung Cancer
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Online Access:http://dx.doi.org/10.3779/j.issn.1009-3419.2025.102.12
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author Xinkai ZOU
Ziyi HE
Yanfei ZHANG
Yi HU
Xiaomin WANG
Zhongjie WU
author_facet Xinkai ZOU
Ziyi HE
Yanfei ZHANG
Yi HU
Xiaomin WANG
Zhongjie WU
author_sort Xinkai ZOU
collection DOAJ
description 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 activation. 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 pathways 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 expression 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 development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.
format Article
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institution Kabale University
issn 1009-3419
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record_format Article
series Chinese Journal of Lung Cancer
spelling doaj-art-2e4c93debcae46759192cb51ef6e19052025-08-20T03:53:51ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872025-04-0128425626610.3779/j.issn.1009-3419.2025.102.12Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung AdenocarcinomaXinkai ZOU0Ziyi HE1Yanfei ZHANG2Yi HU3Xiaomin WANG4Zhongjie WU5Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing 314000, ChinaJiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing 314000, ChinaDepartment of Cardiothoracic Surgery, 
The First Hospital of Jiaxing, Jiaxing 314000, ChinaDepartment of Cardiothoracic Surgery, 
The First Hospital of Jiaxing, Jiaxing 314000, ChinaDepartment of Cell Biology, College of Medicine, Jiaxing University, Jiaxing 314000, ChinaDepartment of Cardiothoracic Surgery, 
The First Hospital of Jiaxing, Jiaxing 314000, ChinaBackground 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 activation. 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 pathways 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 expression 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 development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.http://dx.doi.org/10.3779/j.issn.1009-3419.2025.102.12lung neoplasmsddb1prognosisbiomarker
spellingShingle Xinkai ZOU
Ziyi HE
Yanfei ZHANG
Yi HU
Xiaomin WANG
Zhongjie WU
Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma
Chinese Journal of Lung Cancer
lung neoplasms
ddb1
prognosis
biomarker
title Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma
title_full Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma
title_fullStr Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma
title_full_unstemmed Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma
title_short Public Database-based Study to Explore the Expression and Role of DDB1 
in Lung Adenocarcinoma
title_sort public database based study to explore the expression and role of ddb1 
in lung adenocarcinoma
topic lung neoplasms
ddb1
prognosis
biomarker
url http://dx.doi.org/10.3779/j.issn.1009-3419.2025.102.12
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