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Abstract

Introduction

Preliminary investigations into the feasibility of Carbamoyl-phosphate synthetase 2, Aspartate transcarbamoylase, and Dihydroorotase (CAD)-targeted therapies have been conducted in a limited range of cancer types in pre-clinical studies. A comprehensive exploration of the diagnostic and prognostic capabilities of CAD, along with an understanding of its underlying biological mechanisms, is needed.

Methods

A range of bioinformatics tools was employed to produce an extensive pan-cancer analysis of CAD expression. Experimental validation of the role of CAD in enzalutamide resistance in prostate cells was conducted. The molecular classification and drug patents of CAD were reviewed using the Worldwide Espacenet ®.

Results

Our study revealed that CAD was upregulated in tumor tissues in most cancer types. The expression of CAD was significantly different in clinical stages, pathological grades, and clinical prognosis. The highest frequency of CAD mutation was shown, but CAD mutations did not affect the clinical outcome of cancer patients. Comprehensive data across different cancer types illustrate the relationship between the expression of CAD and tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD). Immune infiltration algorithms showed a positive link between CAD level and the prevalence of tumor-associated fibroblasts, MDSC, mast cells, and CD4+T cells. CAD level was positively linked to the immune checkpoint, suggesting a potential synergistic effect between CAD and immunotherapy. The GSEA analysis revealed that CAD expression is significantly associated with angiogenesis and epithelial-mesenchymal transition (EMT) pathways. Finally, we demonstrated that knockdown of CAD inhibits the growth of prostate cancer (PCa) cells and resistance to enzalutamide.

Discussion

Our pan-cancer analysis revealed that CAD upregulation correlated with poor prognosis, genomic instability, and an immunosuppressive microenvironment. Functionally, CAD promoted prostate cancer cell proliferation and drove enzalutamide resistance. Targeting CAD suppressed tumor growth and overcame drug resistance, highlighting its potential as a therapeutic target and prognostic biomarker in cancer.

Conclusion

This study revealed the diagnostic and prognostic potential of CAD. Notably, CAD exhibits essential functions in PCa cell proliferation and enzalutamide resistance.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-10-29
2025-12-17

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CAD is Associated with Cancer Prognosis and Promotes Enzalutamide Resistance in Prostate Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0115748928412596251011092220
/content/journals/pra/10.2174/0115748928412596251011092220
/content/journals/pra/10.2174/0115748928412596251011092220
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  • Article Type:     Research Article
Keywords: prognosis ; enzalutamide resistance ; immune infiltration ; pan-cancer ; CAD ; prostate cancer

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