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已发表论文
通过两样本孟德尔随机化分析探究调节性 T 细胞与光化性角化病之间的因果关联
Authors Li H, Zhong J, Bi C, Chen Q , Deng H, Ou S, Chen J, Zou H, Lin T, Zhu H
Received 3 June 2025
Accepted for publication 30 August 2025
Published 4 November 2025 Volume 2025:18 Pages 2895—2906
DOI https://doi.org/10.2147/CCID.S543632
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Monica K. Li
Huaping Li,1,2,* Jinbao Zhong,1,2,* Chao Bi,1,2 Quan Chen,1,2 Huiyan Deng,1,2 Shanshan Ou,1,2 Jiaoquan Chen,1,2 Hui Zou,1,2 Tianyi Lin,1,2 Huilan Zhu1,2
1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China; 2Institute of Dermatology, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Huilan Zhu, Email zhlhuilan@126.com
Purpose: Actinic keratosis is a highly prevalent precancerous skin condition and a major risk factor for cutaneous squamous cell carcinoma with a significant risk of malignant transformation. Despite its clinical importance, the causal role of immune factors, especially regulatory T (Treg) cells, in actinic keratosis pathogenesis remains unclear. A two-sample Mendelian Randomization (MR) approach was employed to investigate the potential causal link between distinct characteristics of Treg cells and the likelihood of developing actinic keratosis.
Patients and Methods: The analysis utilized publicly available genetic data on 167 Treg cell traits and actinic keratosis risk. The Inverse Variance Weighted (IVW) method was the primary analytical approach, supported by MR-Egger, weighted median, and weighted mode analyses. Sensitivity of the findings was assessed through Cochran’s Q test, MR-Egger analysis, the MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out tests.
Results: The IVW analysis revealed a significant association between resting Treg cell activity and actinic keratosis (OR: 0.9997, p = 0.0420). Additional significant associations included CD39+ resting Treg percentage of CD4 Tregs (OR: 0.9998, p = 0.0123), CD28- double negative (DN) Treg percentage (OR: 0.9995, p = 0.0359), and CD28+ CD45RA- CD8dim Tregs (OR: 1.0002, p = 0.0312). No significant associations were found in supplementary analyses, but sensitivity tests confirmed the reliability of the results.
Conclusion: This study suggests a potential causal relationship between certain Treg cell traits and the risk of actinic keratosis, indicating that further research is needed to clarify the underlying mechanisms of this association.
Keywords: actinic keratosis, regulatory T cells, immunity, Mendelian randomization, GWAS
1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China; 2Institute of Dermatology, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Huilan Zhu, Email zhlhuilan@126.com
Purpose: Actinic keratosis is a highly prevalent precancerous skin condition and a major risk factor for cutaneous squamous cell carcinoma with a significant risk of malignant transformation. Despite its clinical importance, the causal role of immune factors, especially regulatory T (Treg) cells, in actinic keratosis pathogenesis remains unclear. A two-sample Mendelian Randomization (MR) approach was employed to investigate the potential causal link between distinct characteristics of Treg cells and the likelihood of developing actinic keratosis.
Patients and Methods: The analysis utilized publicly available genetic data on 167 Treg cell traits and actinic keratosis risk. The Inverse Variance Weighted (IVW) method was the primary analytical approach, supported by MR-Egger, weighted median, and weighted mode analyses. Sensitivity of the findings was assessed through Cochran’s Q test, MR-Egger analysis, the MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out tests.
Results: The IVW analysis revealed a significant association between resting Treg cell activity and actinic keratosis (OR: 0.9997, p = 0.0420). Additional significant associations included CD39+ resting Treg percentage of CD4 Tregs (OR: 0.9998, p = 0.0123), CD28- double negative (DN) Treg percentage (OR: 0.9995, p = 0.0359), and CD28+ CD45RA- CD8dim Tregs (OR: 1.0002, p = 0.0312). No significant associations were found in supplementary analyses, but sensitivity tests confirmed the reliability of the results.
Conclusion: This study suggests a potential causal relationship between certain Treg cell traits and the risk of actinic keratosis, indicating that further research is needed to clarify the underlying mechanisms of this association.
Keywords: actinic keratosis, regulatory T cells, immunity, Mendelian randomization, GWAS