Martin-Martin, Natalia (N);Garcia-Longarte, Saioa (S);Corres-Mendizabal, Jon (J);Lazcano, Uxue (U);Astobiza, Ianire (I);Bozal-Basterra, Laura (L);Herranz, Nicolas (N);van Splunder, Hielke (H);Carlevaris, Onintza (O);Pujana-Vaquerizo, Mikel (M);Blasco, María Teresa (MT);Aransay, Ana M (AM);Rosino, Antonio (A);Tudela, Julian (J);Jimenez, Daniel (D);Martinez, Alberto (A);Salca, Andrei (A);Santos-Martín, Aida (A);Rey, Sofía (S);Ugalde-Olano, Aitziber (A);Gonzalo, David (D);Graupera, Mariona (M);Gomis, Roger R (RR);Mateo, Joaquin (J);Unda, Miguel (M);Gonzalez-Billalabeitia, Enrique (E);Loizaga-Iriarte, Ana (A);Mendizabal, Isabel (I);Carracedo, Arkaitz (A);

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Genome Biol.2025 Jun 03;26(1):154.doi:10.1186/s13059-025-03623-5

Abstract

BACKGROUND: Metastatic hormone-naïve prostate cancer (mHNPC) is an infrequent form of this tumor type that is characterized by metastasis at the time of diagnosis and accounts for up to 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration-resistant prostate cancer, the molecular characteristics of mHNPC remain largely unexplored.

RESULTS: Here, we provide the first extensive transcriptomics characterization of primary tumor specimens from patients with mHNPC. We generate discovery and validation bulk and single-cell RNA-seq datasets and perform integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodeling as a predominant feature of these tumors. Importantly, we discover a central role for the SRY-box transcription factor 11 (SOX11) in triggering a heterotypic communication that is associated with the acquisition of metastatic properties.

CONCLUSIONS: Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.