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已发表论文
WRN泛癌分析：从多组学生物标志物发现到指导治疗的功能证据
Authors Yao QQ, Qi Y, Shi PQ, Yang ZY, Qu P, Zhang WW
Received 1 September 2025
Accepted for publication 13 January 2026
Published 29 January 2026 Volume 2026:19 564441
DOI https://doi.org/10.2147/OTT.S564441
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Yong Teng
Qing-Qing Yao,1 Yue Qi,2 Pei-Qin Shi,3 Zi-Ye Yang,1 Pengpeng Qu,1,4 Wen-Wen Zhang4
1Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Clinical School of Obstetrics and Gynecology Center, Tianjin Medical University, Tianjin, People’s Republic of China; 4Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, Tianjin, People’s Republic of China
Correspondence: Wen-Wen Zhang, Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, Tianjin, People’s Republic of China, Email zhangsmell2@hotmail.com Pengpeng Qu, Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, School of Medicine, Nankai University, Tianjin, People’s Republic of China, Email qu.pengpeng@hotmail.com
Background: The RecQ DNA helicase family member WRN is an important protein for maintaining genome stability. The concept of attention as a synthetic lethal target for MSI-H tumors has garnered significant attention in recent years. However, the role of WRN in cancer development, diagnosis, and prognosis has not yet been systematically evaluated at the pan-cancer level.
Methods: On the basis of multiple public cancer databases, we employed bioinformatics techniques to systematically assess WRN expression, variation, and interaction pathways across various cancers, along with the impact of WRN expression on immune profiling, drug sensitivity, and treatment, as a diagnostic tool. Additionally, we used three cancer cell lines to evaluate the suppressor function of WRN inactivation.
Results: WRN is highly expressed in rapidly proliferating tissues and is dysregulated in a cancer-specific manner, particularly in tumors with hereditary DNA repair deficiencies and myeloid malignancies. WRN expression and variants are correlated with prognosis and immune activation potential in cancers. In digestive cancer and endometrial cancer with a high proportion of MSI-H tumors, WRN is positively associated with MSI/TMB signatures. Pharmacogenomic analyses revealed significant correlations between WRN expression levels and sensitivity to the DNA synthesis inhibitors PI3K, ALK, and IFG1R and other target agents and immunomodulators. In vitro validation using WRN inhibitors demonstrated potent suppression of malignant phenotypes (proliferation, clonogenicity, migration, invasion) in colorectal, endometrial, and ovarian cancer models.
Conclusion: Our study suggests that WRN plays a role in cancer diagnosis and therapy, especially in cancers characterized by replicative stress or defective DNA damage repair, and that WRN can serve as a potential target for cancer immunotherapy or targeted therapies and as a prognostic marker for certain tumors.
Keywords: WRN, diagnostic marker, tumor target therapy, genomic instability, pan-cancer analysis
1Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Clinical School of Obstetrics and Gynecology Center, Tianjin Medical University, Tianjin, People’s Republic of China; 4Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, Tianjin, People’s Republic of China
Correspondence: Wen-Wen Zhang, Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, Tianjin, People’s Republic of China, Email zhangsmell2@hotmail.com Pengpeng Qu, Department of Gynecological Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, School of Medicine, Nankai University, Tianjin, People’s Republic of China, Email qu.pengpeng@hotmail.com
Background: The RecQ DNA helicase family member WRN is an important protein for maintaining genome stability. The concept of attention as a synthetic lethal target for MSI-H tumors has garnered significant attention in recent years. However, the role of WRN in cancer development, diagnosis, and prognosis has not yet been systematically evaluated at the pan-cancer level.
Methods: On the basis of multiple public cancer databases, we employed bioinformatics techniques to systematically assess WRN expression, variation, and interaction pathways across various cancers, along with the impact of WRN expression on immune profiling, drug sensitivity, and treatment, as a diagnostic tool. Additionally, we used three cancer cell lines to evaluate the suppressor function of WRN inactivation.
Results: WRN is highly expressed in rapidly proliferating tissues and is dysregulated in a cancer-specific manner, particularly in tumors with hereditary DNA repair deficiencies and myeloid malignancies. WRN expression and variants are correlated with prognosis and immune activation potential in cancers. In digestive cancer and endometrial cancer with a high proportion of MSI-H tumors, WRN is positively associated with MSI/TMB signatures. Pharmacogenomic analyses revealed significant correlations between WRN expression levels and sensitivity to the DNA synthesis inhibitors PI3K, ALK, and IFG1R and other target agents and immunomodulators. In vitro validation using WRN inhibitors demonstrated potent suppression of malignant phenotypes (proliferation, clonogenicity, migration, invasion) in colorectal, endometrial, and ovarian cancer models.
Conclusion: Our study suggests that WRN plays a role in cancer diagnosis and therapy, especially in cancers characterized by replicative stress or defective DNA damage repair, and that WRN can serve as a potential target for cancer immunotherapy or targeted therapies and as a prognostic marker for certain tumors.
Keywords: WRN, diagnostic marker, tumor target therapy, genomic instability, pan-cancer analysis