Clonal Evolution and Transcriptional Plasticity Shape Metastatic Dissemination Routes in Prostate Cancer DOI
Joachim Weischenfeldt, Migle Mikutenaite,

Evdoxia Karadoulama

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Abstract Prostate cancer is a highly heterogeneous disease, driven by genomic and transcriptional changes that impact disease progression metastatic potential. The interplay between clonal evolution, plasticity the tumour microenvironment within prostate gland is, however, poorly understood. Here, we leveraged integrated single-nuclei RNA sequencing whole-genome from 43 spatially distinct samples five patients with advanced to reconstruct evolution trajectories driving metastasis at single-cell resolution. We find extensive heterogeneity, including both monophyletic polyphyletic dissemination, ongoing in primary after spread. Metastatic seeding converged on involving changes, androgen receptor independence activation of estrogen-, WNT- JAK/STAT- pathway activity, areas. Our findings suggest an intricate cellular point toward more integrative prognostic markers for improved patient management.

Language: Английский

Clonal Evolution and Transcriptional Plasticity Shape Metastatic Dissemination Routes in Prostate Cancer DOI
Joachim Weischenfeldt, Migle Mikutenaite,

Evdoxia Karadoulama

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Abstract Prostate cancer is a highly heterogeneous disease, driven by genomic and transcriptional changes that impact disease progression metastatic potential. The interplay between clonal evolution, plasticity the tumour microenvironment within prostate gland is, however, poorly understood. Here, we leveraged integrated single-nuclei RNA sequencing whole-genome from 43 spatially distinct samples five patients with advanced to reconstruct evolution trajectories driving metastasis at single-cell resolution. We find extensive heterogeneity, including both monophyletic polyphyletic dissemination, ongoing in primary after spread. Metastatic seeding converged on involving changes, androgen receptor independence activation of estrogen-, WNT- JAK/STAT- pathway activity, areas. Our findings suggest an intricate cellular point toward more integrative prognostic markers for improved patient management.

Language: Английский

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