The transcriptional landscape of metastatic hormone-naive prostate cancer

Natalia Martín-Martín; Saioa Garcia‐Longarte; Jon Corres-Mendizabal; Uxue Lazcano; Ianire Astobiza; Laura Bozal‐Basterra; Nicolás Herranz; Hielke van Splunder; Onintza Carlevaris; Mikel Pujana-Vaquerizo; María Teresa Blasco; Ana María Aransay; Antonio Rosino; Julián Tudela; Daniel Jimenez; Alberto Martinez; Andrei Salca; Aida Santos-Martín; Sofía Rey; Aitziber Ugalde‐Olano; David Gonzalo; Mariona Graupera; Roger R. Gomis; Joaquı́n Mateo; Miguel Unda; Enrique González‐Billalabeitia; Ana Loizaga‐Iriarte; Isabel Mendizabal; Arkaitz Carracedo

doi:10.1186/s13059-025-03623-5

Cancer BiologyGenome biologyJun 3, 2025

Peer-reviewed journal article

The transcriptional landscape of metastatic hormone-naive prostate cancer

Natalia Martín-Martín iD, Saioa Garcia‐Longarte iD, Jon Corres-Mendizabal iD, Uxue Lazcano iD, Ianire Astobiza iD, Laura Bozal‐Basterra iD, Nicolás Herranz iD, Hielke van Splunder, Onintza Carlevaris iD, Mikel Pujana-Vaquerizo iD, María Teresa Blasco iD, Ana María Aransay iD, Antonio Rosino iD, Julián Tudela, Daniel Jimenez, Alberto Martinez, Andrei Salca iD, Aida Santos-Martín, Sofía Rey, Aitziber Ugalde‐Olano, David Gonzalo, Mariona Graupera iD, Roger R. Gomis iD, Joaquı́n Mateo iD, Miguel Unda iD, , Arkaitz Carracedo iD

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Abstract

Metastatic hormone-naive prostate cancer (mHNPC) is an infrequent form of this tumour type that is characterized by metastasis at the time of diagnosis and accounts for 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration resistant prostate cancer (mCRPC), the molecular characteristics of mHNPC remain largely unexplored. Here we provide the first extensive transcriptomics characterization of mHNPC. We generated discovery and validation bulk and single-cell RNA-Seq datasets and performed integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodelling as a predominant feature of these tumours. Importantly, we discover a central role for the transcription factor SOX11 in triggering a heterotypic communication that is associated to the acquisition of metastatic properties. Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.