Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination

Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination

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...

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Main Authors: Natalia Martin-Martin, Saioa Garcia-Longarte, Jon Corres-Mendizabal, Uxue Lazcano, Ianire Astobiza, Laura Bozal-Basterra, Nicolas Herranz, Hielke van Splunder, Onintza Carlevaris, Mikel Pujana-Vaquerizo, María Teresa Blasco, Ana M. Aransay, Antonio Rosino, Julian Tudela, Daniel Jimenez, Alberto Martinez, Andrei Salca, Aida Santos-Martín, Sofía Rey, Aitziber Ugalde-Olano, David Gonzalo, Mariona Graupera, Roger R. Gomis, Joaquin Mateo, Miguel Unda, Enrique Gonzalez-Billalabeitia, Ana Loizaga-Iriarte, Isabel Mendizabal, Arkaitz Carracedo
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Genome Biology
Subjects:
Prostate cancer
Metastatic driver
Cancer cell reprogramming
Single-cell transcriptomics
Hormone-naïve
Tumor-stromal heterotypic communication
Online Access:https://doi.org/10.1186/s13059-025-03623-5
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Summary: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.
ISSN:1474-760X

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