{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293911/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293911"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A Unique System of Paired PDX Models to Investigate the Progression of Potentially Lethal to Lethal Prostate Tumors at a Multi-omic Level","description":"Prostate cancer (PCa) exhibits substantial heterogeneity in aggressiveness among patients, with significant lethality in its advanced metastatic stages. Defining the molecular mechanisms underlying rapid disease progression remains a pressing unmet need. Here, we present a comparative analysis of a longitudinally paired patient-derived xenograft model of aggressive PCa progression before and after therapeutic intervention. Using multi-omic analysis, we characterized the MDA PCa 177-B (androgen receptor [AR]-negative, basal) and MDA PCa 189-1 (AR-positive, luminal) models, which exhibit distinct transcriptomic profiles yet originate from a shared clonal lineage. Targeted and single-cell DNA sequencing revealed that these models share 71.5% of copy number variations, tracing back to a common ancestral cell population. Targeted bisulfite sequencing of both models revealed epigenetic marks unique for aggressive disease compared to normal/benign prostate. 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.","dates":{"publication":"2026/04/05"},"accession":"GSE293911","cross_references":{"GSM":["GSM8893244","GSM8893245"],"GPL":["24676"],"GSE":["293911"],"taxon":["Homo sapiens"]}}