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Beitragstitel The landscape of stemness-associated markers in the development of castrationresistant prostate cancer
Beitragscode P057
Autor:innen
  1. Joël Federer-Gsponer University Hospital Basel Präsentierende:r
  2. David C. Müller Universtitätsspital Basel und Universität Basel
  3. Tobias Zellweger St. Claraspital Basel
  4. Christian Ruiz Universitätsspital Basel
  5. Lukas Bubendorf Universitätsspital Basel
  6. Clémentine Le Magnen Universitätsspital Basel
  7. Helge Seifert Universitätsspital Basel
  8. Cyrill A. Rentsch Universitätsspital Basel
Präsentationsform moderierte Poster
Themengebiete
  • Grundlageforschung
Abstract-Text Background and objectives
Distinct stem-like cell populations have been identified based on their ability to initiate and
drive prostate cancer (PCa) recurrence following castration in mouse-based models. Yet the
relevance of these populations in the course of the human disease and particularly for the
transition from hormone naive to castration-resistance is unclear. Here we aimed at
deciphering the prognostic and clinical significance of putative stem cell markers in PCa
progression.
Materials and Methods
We constructed a tissue microarray (TMA) comprising 118 matched hormone-naive (HN) and
castration-resistant (CR) tissues specimens derived from 57 PCa patients and including
transurethral resections and few distant metastases. Expression of eight stem-associated
markers (ALDH1A1, ALDH1A3, ALDH3A1, BMI1, NANOG, NKX3.1, POU5F1, SOX2) was
assessed by immunohistochemistry and scored as percentage of positive cells. The resulting
scores were statistically analyzed and compared to pathological and clinical data associated
with the samples. Publicly available transcriptional datasets were interrogated to assess the
expression of the factors in silico.
Results
Immunohistochemical assessment of paired tissue samples revealed atypical patterns of
expression and remarkable intra- and inter-tumor heterogeneity for most of the investigated
markers. Notably, none of the markers showed significant changes in expression upon the
development of castration resistance (CR vs. HN). Using unsupervised clustering approaches,
we identified phenotypic subtypes based on the expression of specific stem-associated
markers. In particular, we observed (i) frequent mutual exclusivity for ALDH1A1 and ALDH1A3
expression, (ii) phenotypic clusters associated with shorter time to castration resistance upon
the initial treatment, and (iii) mutual exclusivity for SOX2 and NKX3.1 in the context of
neuroendocrine differentiation. In silico analyses of publicly available gene expression
datasets supported similar findings at the transcriptomic level.
Conclusions
Our findings pave the way for futures studies aimed at further exploring the clinical implication
and the functional relevance of stem-like cell populations in PCa progression.