| Autor: |
Kimmo Kettunen, Julia Mathlin, Tarja Lamminen, Asta Laiho, Merja R. Häkkinen, Seppo Auriola, Laura L. Elo, Peter J. Boström, Matti Poutanen, Pekka Taimen |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 108, Iss , Pp 105359- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2024.105359 |
| Popis: |
Summary: Background: Bladder cancer is a highly over-represented disease in males. The involvement of sex steroids in bladder carcinogenesis and the utilisation of steroid hormone action as a therapeutic target have been frequently proposed. However, the intratumoural steroid milieu remains unclear. Methods: We used mass spectrometry and transcriptomic profiling to determine the levels of 23 steroid hormones and the expression of steroidogenic enzymes in primary tumours from patients who underwent transurethral resection (n = 24), and tumours and adjacent morphologically benign bladder tissues from treatment-naïve patients, who underwent radical cystectomy (n = 20). The corresponding steroids were determined from the patients’ sera. Findings: Our results show that both bladder tumours and non-tumour tissues are androgen-poor, with DHT being virtually unquantifiable and testosterone at castration levels. Intratumoural enzymes that inactivate potent androgens (e.g., HSD17B2) exhibited similar tumour aggressiveness-linked downregulation, as reported in advanced forms of classical steroid-dependent cancers, whereas there was little change in the corresponding activating enzymes. Finally, our results suggest cancer aggressiveness-linked dissimilarities in steroid profiles; the patients with overall low circulating steroid levels and those with an association between androgen receptor expression and intratumoural testosterone levels in place had fewer recurrences than the rest. Interpretation: By revealing the steroid landscape of bladder cancer, our study not only underscores the androgen-poor nature of the malignancy but also identifies potential alterations in steroid profiles that are linked to disease aggressiveness. Funding: The Cancer Foundation Finland, the Finnish State Research Funding (VTR). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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