Comparison between human umbilical vein endothelial cell and prostate cancer TMPRSS2 (transmembrane protease, serine-2):ERG fusion-positive human prostate epithelial cancer cell line (VCaP) cells revealed distinctive lineage-specific transcriptome and super-enhancer profiles.
Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P = 0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%, P = 0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC-P) (10.0% vs 18.6%, P = 0.012).
In summary, SPDEF overexpression was associated with aggressive behaviour, particularly in ERG negative prostate cancer, and may have potential for clinical application.
Our results identified ERG as the strongest predictor for BCR and showed that potential prognostic prostate cancer biomarkers can be identified from FFPE tumor specimens.
Here, we analyzed the immunohistochemical expression of CEBPA in a tissue microarray containing more than 17 000 prostate cancer specimens with annotated clinical and molecular data including for example TMPRSS2:ERG fusion and PTEN deletion status.
First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG.
Dual-label species (ie, human vs mouse) specific centromere and telomere Fluorescence In Situ Hybridization (FISH) and immuno-histochemical (IHC) staining of tissue microarrays (TMAs) containing replicates of the PDX models were used for characterization of expression of a number of phenotypic markers important for prostate cancer including AR (assessed by IHC and FISH), Ki67, vimentin, RB1, P-Akt, chromogranin A (CgA), p53, ERG, PTEN, PSMA, and epithelial cytokeratins.
Kaplan-Meir plots and long rank tests were used to assess the association of ERG and PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer.
In conclusion the combination of pro-NPY and ERG expression did not show association with risk of BF, castration-based treatment, CRPC, and PCa-specific death following RP.
According to the above-mentioned four pathways, the following markers of response were identified: transcription of the oncogene TMPRSS2:ERG, translation of Aurora-A, coding of β1C integrin gene, translation of Ki-67, expression of nerve growth factors TrkA and p75NGFR, anti-angiogenic activity and micro-vessel density were involved into suppression of proliferation; mRNA transcription of bcl-2, expression of cleaved caspase-3 and translation of insulin growth factor binding protein 3, into induction of apoptosis; expression of IL-7 gene, programmed death-ligand 1, and increase of intra-prostatic T-cell population were related to alteration of immune response; finally, expression of heat shock protein 27 and de-differentiation of PCa to neuroendocrine cells, influenced the onset of hormonal refractoriness.
Author Correction: Up regulation and nuclear translocation of Y-box binding protein 1 (YB-1) is linked to poor prognosis in ERG-negative prostate cancer.
We found that elevated T2:ERG and PCA3 levels were positively associated with high-risk PCa and obtained a corresponding area-under-the-curve values of 0.790 and 0.833 for predicting PCa and high-risk PCa on biopsy, respectively.
Importantly, androgens exert a major role in PCa formation and progression and one of the hypothesized mechanism proposed has been linked to the chromosomal rearrangement of the androgen regulated gene TMPRSS2 with ERG.
<i>TMPRSS2:ERG</i> status was assessed by IHC for presence of ERG on archival tumor specimens for 912 patients with prostate cancer, of whom 48% were ERG-positive.<b>Results:</b> In multivariable models, we found no association between regular use of aspirin and risk of <i>ERG</i>-positive prostate cancer (HR, 1.02; 95% confidence interval, 0.85-1.23), nor any association with duration or frequency of aspirin use.