A Unique System of Paired PDX Models to Investigate the Progression of Potentially Lethal to Lethal Prostate Tumors at a Multi-omic Level

Next, through single-cell RNA sequencing, we identified a subset of cells exhibiting a low differentiation profile, present in both PDX models and characterized by a unique molecular signature associated with adaptive immune responses and metastasis-related pathways. Further integrative analysis using data from a broad spectrum of disease samples demonstrated that, within this pair of aggressive PDX models, these low-differentiation clusters are exclusive to stem-like tumor cell populations.

These findings support the hypothesis that a continuum of epigenetic, transcriptomic, and phenotypic transitions occurs during the progression of PCa from its potentially lethal to lethal stages. We suggest that this continuum can be captured through well-characterized, longitudinal PDX models derived from the same patient. Our multi-omic approach underscores the value of such models in uncovering the dynamic and adaptive mechanisms of PCa aggressiveness.