Distribution of Molecular Subtypes in Muscle-invasive Bladder Cancer Is Driven by Sex-specific Differences.

de Jong, Joep J; Boormans, Joost L; van Rhijn, Bas W G; Seiler, Roland; Boorjian, Stephen A; Konety, Badrinath; Bivalacqua, Trinity J; Wheeler, Thomas; Svatek, Robert S; Douglas, James; Wright, Jonathan; Dall'Era, Marc; Crabb, Simon J; Efstathiou, Jason A; van der Heijden, Michiel S; Mouw, Kent W; Miyamoto, David T; Lotan, Yair; Black, Peter C; Gibb, Ewan A; ... (2020). Distribution of Molecular Subtypes in Muscle-invasive Bladder Cancer Is Driven by Sex-specific Differences. (In Press). European urology oncology Elsevier 10.1016/j.euo.2020.02.010

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Muscle-invasive bladder cancer (MIBC) is a sex-biased cancer with a higher incidence in men but worse outcomes in women. The root cause behind these observations remains unclear. To investigate whether sex-specific tumor biology could explain the differences in clinical behavior of MIBC, we analyzed the transcriptome profiles from transurethral resected bladder tumors of 1000 patients. Female tumors expressed higher levels of basal- and immune-associated genes, while male tumors expressed higher levels of luminal markers. Using molecular subtyping, we found that the rates of the basal/squamous subtype were higher in females than in males. Males were enriched with tumors of the luminal papillary (LumP) and neuroendocrine-like subtypes. Male MIBC tumors had higher androgen response activity across all luminal subtypes and male patients with LumP tumors were younger. Taken together, these data confirm differences in molecular subtypes based on sex. The role of the androgen response pathway in explaining subtype differences between men and women should be studied further. PATIENT SUMMARY: We explored the sex-specific biology of bladder cancer in 1000 patients and found that women had more aggressive cancer with higher immune activity. Men tended toward less aggressive tumors that showed male hormone signaling, suggesting that male hormones may influence the type of bladder cancer that a patient develops.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Seiler-Blarer, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2588-9311

Publisher:

Elsevier

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

23 Jun 2020 14:07

Last Modified:

23 Jun 2020 14:14

Publisher DOI:

10.1016/j.euo.2020.02.010

PubMed ID:

32205136

Uncontrolled Keywords:

Bladder cancer Gene expression Molecular subtypes Sex specific

BORIS DOI:

10.7892/boris.144422

URI:

https://boris.unibe.ch/id/eprint/144422

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