Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination
Martin-Martin N, Garcia-Longarte S, Corres-Mendizabal J, Lazcano U, Astobiza I, Bozal-Basterra L, Herranz N, van Splunder H, Carlevaris O, Pujana-Vaquerizo M, Blasco MT, Aransay AM, Rosino A, Tudela J, Jimenez D, Martinez A, Salca A, Santos-Martín A, Rey S, Ugalde-Olano A, Gonzalo D, Graupera M, Gomis RR, Mateo J, Unda M, Gonzalez-Billalabeitia E, Loizaga-Iriarte A, Mendizabal I, Carracedo A.
Genome Biol
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.
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