Molecular Subtyping of Primary Prostate Cancer Reveals Specific and Shared Target Genes of Different ETS Rearrangements

Purpose: To study the diagnostic value of PET-CT with 68Ga-PSMA-11 in the diagnosis of a primary prostate cancer, preoperative staging, and the detection of recurrence of prostate cancer (PCa). Methods: 28 patients aged 64.7 ± 8.74 years were included. 10 patients primary prostate cancer, and 18 patients with biochemical recurrence of the disease after radical treatment were examined. All patients underwent PET-CT with 68Ga-PSMA-11 according the whole body protocol. Interpretation of images was performed visually and quantitatively by calculation of SUL max. Results: High focal or diffuse 68Ga-PSMA-11 uptake was found in prostate parenchyma in patients with primary prostate cancer. Additionally metastases in regional lymph nodes were diagnosed in 4 patients and bone metastases were found in one patient. The correlation between 68Ga-PSMA-11 uptake level and Gleason index in the primary tumor (R Spearmen = 0.25, p = 0.57) was not observed. PET-positive results were obtained in 14 patients and PET-negative results in 4 patients with biochemical recurrence of PCa. The relationship between the frequency of PET-positive results and Gleason index was not revealed (R Spearmen = 0.2, p = 0.39). We found a weak but significant correlation between the frequency of PET-positive results and the prostate tumor stage according to the T category (R Spearmen = 0.49, p = 0.049). In patients with low values of PSA (less than 1.0 ng/ml) in 4 out of 9 cases, PET-negative results were obtained. In patients with PSA level more than 1.0 ng/ml PET-positive results were obtained in all cases. Conclusions: PET/CT with 68Ga-PSMA-11 allows to diagnose the primary prostate cancer, to establish the stage of the disease in categories N and M, and also to determine the localization and dissemination of the tumor in patients with biochemical recurrence of prostate cancer. The relationship between 68Ga-PSMA-11 uptake in primary tumor and Gleason index was not found. The probability of obtaining PET-positive results in cases of biochemical recurrence is affected by a PSA level above 1 ng/ml and a high stage of the disease according to the T category (T3-T4).

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Imaging Primary Prostate Cancer and Bone Metastasis

10.21236/ada472718 ◽

2007 ◽

Author(s):

Xiaoyuan Chen

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Primary Prostate Cancer

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The Role of Androgen Receptor-Target Genes in Racial Disparity of Prostate Cancer

10.21236/ada502368 ◽

2007 ◽

Author(s):

Patrice S. Pearce

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Racial Disparity ◽

Target Genes

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Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

European Urology ◽

10.1016/j.eururo.2021.03.017 ◽

2021 ◽

Author(s):

Carissa E. Chu ◽

Mohammed Alshalalfa ◽

Martin Sjöström ◽

Shuang G. Zhao ◽

Yang Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Features ◽

Molecular Subtypes ◽

Prostate Specific Membrane Antigen ◽

Primary Prostate Cancer ◽

Specific Membrane

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Transcriptional landscape of PTEN loss in primary prostate cancer

BMC Cancer ◽

10.1186/s12885-021-08593-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Eddie Luidy Imada ◽

Diego Fernando Sanchez ◽

Wikum Dinalankara ◽

Thiago Vidotto ◽

Ericka M. Ebot ◽

...

Keyword(s):

Prostate Cancer ◽

Meta Analysis ◽

Pten Loss ◽

Primary Prostate Cancer ◽

Expression Atlas ◽

Transcriptomic Signature ◽

Transcriptional Changes ◽

New Biomarkers ◽

Adaptive Immune Systems ◽

Transcriptional Landscape

Abstract Background PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa. Methods Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas. Results The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression. Conclusion We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.

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Chromatin-directed proteomics-identified network of endogenous androgen receptor in prostate cancer cells

Oncogene ◽

10.1038/s41388-021-01887-2 ◽

2021 ◽

Author(s):

Kaisa-Mari Launonen ◽

Ville Paakinaho ◽

Gianluca Sigismondo ◽

Marjo Malinen ◽

Reijo Sironen ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Protein A ◽

Chorioallantoic Membrane ◽

Chromatin Accessibility ◽

Castration Resistant Prostate Cancer ◽

Novel Therapy ◽

Mesenchymal Transition

AbstractTreatment of prostate cancer confronts resistance to androgen receptor (AR)-targeted therapies. AR-associated coregulators and chromatin proteins hold a great potential for novel therapy targets. Here, we employed a powerful chromatin-directed proteomics approach termed ChIP-SICAP to uncover the composition of chromatin protein network, the chromatome, around endogenous AR in castration resistant prostate cancer (CRPC) cells. In addition to several expected AR coregulators, the chromatome contained many nuclear proteins not previously associated with the AR. In the context of androgen signaling in CRPC cells, we further investigated the role of a known AR-associated protein, a chromatin remodeler SMARCA4 and that of SIM2, a transcription factor without a previous association with AR. To understand their role in chromatin accessibility and AR target gene expression, we integrated data from ChIP-seq, RNA-seq, ATAC-seq and functional experiments. Despite the wide co-occurrence of SMARCA4 and AR on chromatin, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, especially those involved in cell morphogenetic changes in epithelial-mesenchymal transition. The depletion also inhibited the CRPC cell growth, validating SMARCA4’s functional role in CRPC cells. Although silencing of SIM2 reduced chromatin accessibility similarly, it affected the expression of a much larger group of androgen-regulated genes, including those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of CRPC cells and tumor size in chick embryo chorioallantoic membrane assay, further emphasizing the importance of SIM2 in CRPC cells and pointing to the functional relevance of this potential prostate cancer biomarker in CRPC cells. Overall, the chromatome of AR identified in this work is an important resource for the field focusing on this important drug target.

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