Epigenome analysis of prostatectomy specimens and samples of prostate cancer bone metastases
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ABSTRACT:
PROVIDER: PRJNA730790 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation profiling of paired samples of non-malignant and malignant prostate tissue obtained from prostatectomy speciments (n=12) and of bone metastasis tissue samples obtained from separate prostate cancer patients (n=70). The Illumina Infinium Methylation EPIC arrays were used to obtain genome-wide DNA methylation profiles across approximately 850,000 CpGs in each sample. The bone metastasis samples were obtained from castration-resistant (n = 52) and untreated (n = 14) prostate cancer patients as well as from prostate cancer patients treated for a short period with castration therapy (n = 4).
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Project description:Proteome characterization of gland confined prostate tumors and non-malignant prostate tissue. Whole cell protein extracts were purified from FFPE radical prostatectomy specimens for a total of 28 tumor samples and 8 adjacent non-malignant prostate tissues. Associated ProteomeXchange identifiers: PXD003430, PXD003452, PXD003515, PXD004132, PXD003615, PXD003636. Quantitative proteomic analysis of adjacent non-malignant prostate tissue (n=8) and gland confined prostate tumors (n=28) obtained from radical prostatectomy procedures; and bone metastatic prostate tumors (n=22) obtained from patients operated to relief spinal cord compression. At the time of surgery, most metastatic patients had relapsed after androgen-deprivation therapy, while 5 were previously untreated.
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Project description:TGF-beta is a known driver of epithelial-mesenchymal transition (EMT) which is associated with tumor aggressiveness and metastasis. However, EMT has not been fully explored in clinical specimens of castration-resistant prostate cancer (CRPC) metastases. To assess EMT in CRPC, gene expression analysis was performed on 149 visceral and bone metastases from 62 CRPC patients and immunohistochemical analysis was performed on 185 CRPC bone and visceral metastases from 42 CRPC patients. In addition, to assess the potential of metastases to seed further metastases the mitochondrial genome was sequenced at different metastatic sites in one patient. TGF-beta was increased in bone versus visceral metastases. While primarily cytoplasmic; nuclear and cytoplasmic Twist were significantly higher in bone than in visceral metastases. Slug and Zeb1 were unchanged, with the exception of nuclear Zeb1 being significantly higher in visceral metastases. Importantly, nuclear Twist, Slug, and Zeb1 were only present in a subset of epithelial cells that had an EMT-like phenotype. Underscoring the relevance of EMT-like cells, mitochondrial sequencing revealed that metastases could seed additional metastases in the same patient. In conclusion, while TGF-beta expression and EMT-associated protein expression is present in a considerable number of CRPC visceral and bone metastases, nuclear Twist, Slug, and Zeb1 localization and an EMT-like phenotype (elongated nuclei and cytoplasmic compartment) was only present in a small subset of CRPC bone metastases. Mitochondrial sequencing from different metastases in a CRPC patient provided evidence for the seeding of metastases from previously established metastases, highlighting the biological relevance of EMT-like behavior in CRPC metastases.
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Project description:DNA-methylation profiles of primary tumors (PT) and paired synchronous lymph node metastases (LN) from Gleason Score (GS)-6/7a (n=20 LN-positive, n=20 LN-negative) and GS-9/10 patients (LN-positive n=20) after prostatectomy and lymphonodectomy were analyzed.
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