Abstract
Condyloma acuminatum (CA), primarily caused by low-risk HPV6/11, is a benign proliferative disease that is difficult to cure and prone to recurrence. However, the molecular and immune mechanisms underlying relapse remain unclear. We combined metabolomic profiling with single-cell RNA sequencing to investigate recurrence-associated changes. Metabolomics revealed dysregulation of ascorbate and aldarate, glycerophospholipid, purine, and arginine/proline metabolism in recurrent CA. Single-cell analysis identified altered expression of metabolism-related genes (AMD1, GSTM3, ALDH3A1, GPX1, GPX4) in keratinocytes, associated with hyperproliferation, impaired differentiation, and ferroptosis resistance. Immune profiling identified transcriptionally distinct myeloid subpopulations in recurrent CA lesions, including M2 macrophages and dendritic cells. KEGG analysis indicated enrichment of antigen processing, phagosome, and endocytosis pathways in M2 macrophages, and antigen processing and viral carcinogenesis in dendritic cells, suggesting altered immune regulatory states. Notably, the key polyamine biosynthesis regulator AMD1 was downregulated in both M2 macrophages and dendritic cells in recurrent lesions, paralleling metabolic evidence of altered arginine-polyamine pathways. These findings suggest that recurrent CA involves coordinated metabolic dysregulation across keratinocytes and immune cells, highlighting potential targets for immunometabolic intervention.
Data availability
All sequencing data supporting the findings of this study have been deposited in the Genome Sequence Archive database under accession number HRA009671 and are available at the following URL: https://ngdc.cncb.ac.cn/gsa-human/s/n6wYVK0Q. Additional data are available from the corresponding author upon reasonable request.
Abbreviations
- CA:
-
Condyloma acuminatum
- HPV:
-
Human papillomavirus
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Acknowledgements
We sincerely thank all the patients and healthy volunteers who generously participated in this study. We are also deeply grateful to all colleagues and collaborators at the Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, for their valuable support throughout the research process. Additionally, we acknowledge the contributions of Hangzhou LC-BIO Co., Ltd., for their technical assistance in sequencing and bioinformatics analysis.
Funding
This study was funded by grants from the Natural Science Foundation of China (82373491, 82471846, 82404156), and Zhejiang Provincial Natural Science Foundation of China (LY24H110001). All authors have reviewed and approved the final manuscript.
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Y.W., Y.X., C.F., J.Z, and Y.S. conceived and designed the study. Y.W., Y.X., S.C., J.P., J.W. and J.C. performed the experiments. Y.X., J.Z., S.C., J.P., J.C., J.W. and C.F. analyzed the data. Y.W., H.C., and J.Z. wrote and reviewed the manuscript. C.H. and M.C. assisted in manuscript revision and figure preparation. Y.S., H.C., and J.Z. assume overall responsibility for the manuscript. J.Z., and H.C., were responsible for supervision and funding acquisition.
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This study was approved by the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Approval No. 20210330-39), and was conducted in accordance with the principles of the Declaration of Helsinki. All procedures involving human participants adhered to the institutional guidelines and were approved by the relevant ethics board. Written informed consent was obtained from all participants prior to their inclusion in the study.
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Wei, Y., Xu, Y., Feng, C. et al. Integrative metabolomic and single-cell transcriptomic analysis of recurrent condyloma acuminatum in humans. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37989-8
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DOI: https://doi.org/10.1038/s41598-026-37989-8
