We report the association of elevated TMPRSS2 expression with increased PrCa risk (independent of a previously-reported risk variant) and with increased tumoral expression of the TMPRSS2:ERG fusion-oncogene in The Cancer Genome Atlas, suggesting a novel germline-somatic interaction mechanism.
Additionally, we revealed such genes for the <i>TMPRSS2-ERG</i> prostate cancer molecular subtype (<i>B4GALNT4</i>, <i>ASRGL1</i>, <i>MYBPC1</i>, <i>RGS11</i>, <i>SLC6A14</i>, <i>GALNT13</i>, and <i>ST6GALNAC1</i>).
Recent advances in genomics and next-generation sequencing heralded the discovery of biomarkers such as the androgen receptor gene (<i>AR</i>) splice events, the <i>TMPRSS2:EGR</i> gene fusion, long noncoding RNA <i>MALAT-1</i> and <i>SCHLAP1</i> for PCa prognosis.
With the advances in deep sequencing technology, a series of new PCa biomarkers have been recently proposed to improve the diagnostic value of PSA, such as prostate cancer antigen 3 (PCA3), TMPRSS2-ETS fusion gene, microRNA, and other regulatory non-coding RNAs.
We also assessed how these two markers correlated with the most common genetic alteration in prostate cancer: TMPRSS2 fusion to ERG (40-60% of carcinomas at the primary site), which places ERG expression under the control of the androgen-regulated TMPRSS2 gene, increasing expression.
Prostate cancer (PCa) tumors harboring translocations of ETS family genes with the androgen responsive TMPRSS2 gene (ETS+ tumors) provide a robust biomarker for detecting PCa in approximately 70% of patients.
Comparison between human umbilical vein endothelial cell and prostate cancerTMPRSS2 (transmembrane protease, serine-2):ERG fusion-positive human prostate epithelial cancer cell line (VCaP) cells revealed distinctive lineage-specific transcriptome and super-enhancer profiles.
The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9.
Only the second study of its kind for the African continent, we support a link between TMPRSS2-ERG status and prostate cancer racial health disparity beyond the borders of the United States.
Higher body mass index (BMI) at baseline (per 5 kg/m<sup>2</sup> HR 0.75; 95% CI, 0.61-0.91; <i>P</i><sub>heterogeneity</sub> = 0.02) and updated BMI over time (per 5 kg/m<sup>2</sup> HR 0.86; 95% CI, 0.74-1.00; <i>P</i><sub>heterogeneity</sub> = 0.07) were associated with a reduced risk of ERG-positive disease only.<b>Conclusions:</b> Our results indicate that anthropometrics may be uniquely associated with <i>TMPRSS2:ERG</i>-positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk.<b>Impact:</b> Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes.
Our study identifies 3p13 deletion as a highly heterogeneous alteration in prostate cancer preferentially developing at rather late stages of progression in <i>TMPRSS2:ERG</i> fusion-positive tumors.
TMPRSS2:ERG is the most frequent gene rearrangement identified in prostate cancer, but whether it is involved in prostate cancer bone metastases is largely unknown.
The <i>TMPRSS2:ERG</i> fusion was expressed in 41% of samples, and the aggressive prostate cancer-associated long noncoding RNA <i>SChLAP1</i> was upregulated in 70%.
Herein, we propose a "mix-to-go" colloidal strategy that utilizes the electrostatic attraction between negatively charged target sequences and positively charged silver nanoparticles (AgNPs) to induce aggregation of AgNPs to profile a panel of clinically validated urinary prostate cancer (PCa) RNA biomarkers ( TMPRSS2:ERG, T2:ERG; prostate cancer antigen 3, PCA3; and kallikrein-related peptidase 2, KLK2).
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.
The TMPRSS2:ERG (T:E) fusion gene is generally believed to be mainly regulated by the activated androgen receptor (AR) signaling in androgen-dependent prostate cancer.
TMPRSS2-ERG-positive and -negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG-positive tumors.
Oncogenic activation of the ETS-related gene (<i>ERG</i>) by recurrent gene fusions (predominantly TMPRSS2-ERG) is one of the most validated and prevalent genomic alterations present in early stages of prostate cancer.
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.