Beitragstitel | The landscape of stemness-associated markers in the development of castrationresistant prostate cancer |
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Beitragscode | P057 |
Autor:innen | |
Präsentationsform | moderierte Poster |
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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. |