Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer

Abstract

Objectives We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy. Materials and Methods Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at two centers; qRT-PCR was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed. Results Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; p< 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared to 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3 and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity). Conclusions A clinical algorithm specifying biopsy for all patients with PSA ≥10ng/ml, while restricting biopsy among those with PSA <10ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer.

Serum CCL11 Levels in Benign Prostatic Hyperplasia and Prostate Cancer

“…Several markers, including prostate-specific membrane antigen, hepsin, a-methylacyl-coenzyme A racemase, telomerase, serine protease TMPRSS2, d-catenin, and prostate-specific non-coding RNA called prostate cancer gene 3 (PCA3, formerly known as DD3), have been identified and tested to date; these markers, when used alone or in combination with serum PSA, have been determined to be variously useful as diagnostic or prognostic markers of PCa [17][18][19][20].…”

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

“…PCA3 (prostate cancer gene 3) in urine is the only Food and Drug Administration (FDA)-approved urinary biomarker of clinical PCa, while the fusion gene TMPRSS2 ERG, α-formyl coenzyme A racemic enzyme (AMACR), single nucleotide polymorphism (SNP), and others have also been reported and confirmed to have correlations with PCa. Therefore, they could be rated as potential PCa biomarkers in urine and may find their way into clinical diagnosis and assessment of therapeutic efficacy (Prensner et al, 2012;Salagierski and Schalken, 2012;Salami et al, 2013;Shipitsin et al, 2014;Wei et al, 2014;Bansal et al, 2015;Frantzi et al, 2015). Recently, prostate born exosomes in urine-called prostasomes-have been used as a promising source of biomarkers (Ronquist and Brody, 1985;Duijvesz et al, 2011;Zijlstra and Stoorvogel, 2016).…”

What are the New Developments in Urinary, Serum and Tissue Biomarkers in Prostate Cancer?

“…Bu skorla gereksiz biyopsilerden kaçınılırken prostat kanseri için daha iyi bir risk sınıflaması yapılabilmektedir. Bu test yaklaşık 2000 idrar örneği ile valide edilmiştir (9,42,43).…”