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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2025-06-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-025-03623-5 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Natalia Martin-Martin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aadc768ef9d149eea54de13238e479f6 |
| institution | OA Journals |
| issn | 1474-760X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj-art-aadc768ef9d149eea54de13238e479f62025-08-20T02:05:38ZengBMCGenome Biology1474-760X2025-06-0126112310.1186/s13059-025-03623-5Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell disseminationNatalia Martin-Martin0Saioa Garcia-Longarte1Jon Corres-Mendizabal2Uxue Lazcano3Ianire Astobiza4Laura Bozal-Basterra5Nicolas Herranz6Hielke van Splunder7Onintza Carlevaris8Mikel Pujana-Vaquerizo9María Teresa Blasco10Ana M. Aransay11Antonio Rosino12Julian Tudela13Daniel Jimenez14Alberto Martinez15Andrei Salca16Aida Santos-Martín17Sofía Rey18Aitziber Ugalde-Olano19David Gonzalo20Mariona Graupera21Roger R. Gomis22Joaquin Mateo23Miguel Unda24Enrique Gonzalez-Billalabeitia25Ana Loizaga-Iriarte26Isabel Mendizabal27Arkaitz Carracedo28Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Vall Hebron Institute of Oncology, Hebron University Hospital CampusEndothelial Pathobiology and Microenviroment Group, Josep Carreras Leukemia Research Institute (IJC)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Cancer Science Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and TechnologyCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Department of Urology, Morales Meseguer University HospitalDepartment of Pathology, Morales Meseguer University HospitalDepartment of Urology, Morales Meseguer University HospitalBiobanco Nodo 3, Morales Meseguer University HospitalVall Hebron Institute of Oncology, Hebron University Hospital CampusDepartment of Urology, Basurto University HospitalDepartment of Urology, Basurto University HospitalDepartment of Pathology, Basurto University HospitalTraslational Prostate Cancer Research Lab, CIC bioGUNE-Basurto, Biobizkaia Health Research Institute Technology ParkCentro de Investigación Biomédica En Red de Cáncer (CIBERONC)Centro de Investigación Biomédica En Red de Cáncer (CIBERONC)Vall Hebron Institute of Oncology, Hebron University Hospital CampusCentro de Investigación Biomédica En Red de Cáncer (CIBERONC)Department of Urology, Morales Meseguer University HospitalCentro de Investigación Biomédica En Red de Cáncer (CIBERONC)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)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.https://doi.org/10.1186/s13059-025-03623-5Prostate cancerMetastatic driverCancer cell reprogrammingSingle-cell transcriptomicsHormone-naïveTumor-stromal heterotypic communication |
| spellingShingle | 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 Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination Genome Biology Prostate cancer Metastatic driver Cancer cell reprogramming Single-cell transcriptomics Hormone-naïve Tumor-stromal heterotypic communication |
| title | Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination |
| title_full | Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination |
| title_fullStr | Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination |
| title_full_unstemmed | Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination |
| title_short | Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination |
| title_sort | transcriptional analysis of metastatic hormone naive prostate cancer primary tumor biopsies reveals a relevant role for sox11 in prostate cancer cell dissemination |
| topic | Prostate cancer Metastatic driver Cancer cell reprogramming Single-cell transcriptomics Hormone-naïve Tumor-stromal heterotypic communication |
| url | https://doi.org/10.1186/s13059-025-03623-5 |
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