Profiling steroid hormone landscape of bladder cancer reveals depletion of intratumoural androgens to castration levels - across-sectional study

Sep 21, 2026

Uploaded by Rowan

Study assesses how steroid hormones vary within bladder tumors and their relationship to cancer aggressiveness. Mass spectrometry and transcriptomic profiling quantify 23 steroid hormones and steroidogenic enzyme expression in primary tumors from transurethral resection patients (n=24) and in tumors plus adjacent benign tissue from radical cystectomy patients (n=20). Serum steroids are also measured. Results show androgen-poor tumor environments, downregulation of androgen-inactivating enzymes, and fewer recurrences in patients with low systemic steroid levels and specific androgen receptor-associated testosterone patterns.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

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Articles Proﬁling steroid hormone landscape of bladder cancer reveals depletion of intratumoural androgens to castration levels: across-sectional study Kimmo Kettunen,a Julia Mathlin,a,b Tarja Lamminen,c Asta Laiho,b Merja R. Häkkinen,d,e Seppo Auriola,e Laura L. Elo,a,b Peter J. Boström,c,i Matti Poutanen,a,f,g,i and Pekka Taimena,h,i,∗ aInstitute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland bTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland cDepartment of Urology and FICAN West Cancer Centre, Turku University Hospital, and University of Turku, Turku, Finland dDepartment of Health Security, Finnish Institute for Health and Welfare, Kuopio, Finland eSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland fDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden gTurku Center for Disease Modeling, University of Turku, Turku, Finland hDepartment of Pathology, Turku University Hospital, Turku, Finland 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) . Copyright © 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)). Keywords: Bladder cancer; Sex steroids; Androgens; Steroid proﬁle; Steroidomics Introduction Male sex is a signiﬁcant risk factor for bladder cancer, with a three-to-four-fold higher incidence in men compared to women.1,2 In contrast, women are more often diagnosed with higher-stage diseases and rare histological subtypes.3,4 Discrepancies in the sex steroid milieu, immune system, and genetic factors are suggested to inﬂuence these sex-linked disparities.3,5 eBioMedicine 2024;108: 105359 Published Online xxx [https://doi.org/10](https://doi.org/10) . 1016/j.ebiom.2024 . 105359 *Corresponding author. Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, Turku, Finland. E-mail address: pekka.taimen@utu.ﬁ (P. Taimen) . iThese authors co-supervised the work equally. [www.thelancet.com Vol](www.thelancet.com Vol)

FAQs

What question does the study address about bladder cancer hormones?

It investigates the intratumoural steroid hormone environment in bladder cancer and whether androgens are depleted to castration-levels, as well as how steroid profiles relate to disease aggressiveness and recurrence.

How were steroid hormones and enzymes measured?

Steroid hormone levels (23 steroids) were quantified using mass spectrometry, while transcriptomic profiling assessed expression of steroidogenic enzymes in primary tumor and benign tissues; matching sera steroids were measured as well.

What did the study find about androgen levels in tumors?

Both bladder tumors and non-tumor tissues were androgen-poor, with DHT virtually unquantifiable and testosterone at castration levels.

Sep 21, 2026

Uploaded by Rowan

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