The prognostic value of Dickkopf-3 (Dkk3), TGFB1 and ECM-1 in prostate cancer.

Autor:	Al Shareef Z; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates., Hachim MY; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates., Bouzid A; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates., Talaat IM; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Faculty of Medicine, Alexandria University, Alexandria, Egypt., Al-Rawi N; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates., Hamoudi R; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.; Division of Surgery and Interventional Science, University College London, London, United Kingdom., Hachim IY; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2024 May 24; Vol. 11, pp. 1351888. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.3389/fmolb.2024.1351888
Abstrakt:	Prostate cancer (PCa) is considered one of the most common cancers worldwide. Despite advances in patient diagnosis, management, and risk stratification, 10%-20% of patients progress to castration-resistant disease. Our previous report highlighted a protective role of Dickkopf-3 (DKK3) in PCa stroma. This role was proposed to be mediated through opposing extracellular matrix protein 1 (ECM-1) and TGF-β signalling activity. However, a detailed analysis of the prognostic value of DKK3, ECM-1 and members of the TGF-β signalling pathway in PCa was not thoroughly investigated. In this study, we explored the prognostic value of DKK3, ECM-1 and TGFB1 using a bioinformatical approach through analysis of large publicly available datasets from The Cancer Genome Atlas Program (TGCA) and Pan-Cancer Atlas databases. Our results showed a significant gradual loss of DKK3 expression with PCa progression ( p < 0.0001) associated with increased DNA methylation in its promoter region ( p < 1.63E-12). In contrast, patients with metastatic lesions showed significantly higher levels of TGFB1 expression compared to primary tumours ( p < 0.00001). Our results also showed a marginal association between more advanced tumour stage presented as positive lymph node involvement and low DKK3 mRNA expression ( p = 0.082). However, while ECM1 showed no association with tumour stage ( p = 0.773), high TGFB1 expression showed a significant association with more advanced stage presented as advanced T3 stage compared to patients with low TGFB1 mRNA expression ( p < 0.001). Interestingly, while ECM1 showed no significant association with patient outcome, patients with high DKK3 mRNA expression showed a significant association with favourable outcomes presented as prolonged disease-specific ( p = 0.0266), progression-free survival ( p = 0.047) and disease-free ( p = 0.05). In contrast, high TGFB1 mRNA expression showed a significant association with poor patient outcomes presented as shortened progression-free ( p = 0.00032) and disease-free survival ( p = 0.0433). Moreover, DKK3, TGFB1 and ECM1 have acted as immune-associated genes in the PCa tumour microenvironment. In conclusion, our findings showed a distinct prognostic value for this three-gene signature in PCa. While both DKK3 and TGFB1 showed a potential role as a clinical marker for PCa stratification, ECM1 showed no significant association with the majority of clinicopathological parameters, which reduce its clinical significance as a reliable prognostic marker. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Al Shareef, Hachim, Bouzid, Talaat, Al-Rawi, Hamoudi and Hachim.)
Databáze:	MEDLINE
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