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Multicenter Study
. 2020 Oct;204(4):691-700.
doi: 10.1097/JU.0000000000001066. Epub 2020 Apr 6.

Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer

J Woo  1 , S Santasusagna  1 , J Banks  2 , S Pastor-Lopez  3 , K Yadav  4 , M Carceles-Cordon  1 , A Dominguez-Andres  1 , R B Den  5   6 , L R Languino  6 , R Pippa  1 , C D Lallas  7 , G Lu-Yao  1 , W K Kelly  1 , K E Knudsen  6 , V Rodriguez-Bravo  6 , A K Tewari  4 , J M Prats  3 , B E Leiby  2 , L G Gomella  7 , Josep Domingo-Domenech  1   6
Affiliations
Multicenter Study

Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer

J Woo et al. J Urol. 2020 Oct.

Abstract

Purpose: Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed in aggressive prostate cancer. We analyzed the predictive value of urine extracellular vesicle GATA2 mRNA alone and in combination with a multigene panel to improve detection of prostate cancer and high risk disease.

Materials and methods: GATA2 mRNA was analyzed in matched extracellular vesicles isolated from urines before and after prostatectomy (16) and paired urine and tissue prostatectomy samples (19). Extracellular vesicle GATA2 mRNA performance to distinguish prostate cancer and high grade disease was tested in training (52) and validation (165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts.

Results: Confirming its prostate origin, urine extracellular vesicle GATA2 mRNA levels decreased significantly after prostatectomy and correlated with prostate cancer tissue GATA2 mRNA levels. In the training and validation cohort GATA2 discriminated prostate cancer (AUC 0.74 and 0.66) and high grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of prostate cancer (AUC 0.84 and 0.72) and high grade cancer (AUC 0.85 and 0.71) in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high grade prostate cancer would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used.

Conclusions: Urine extracellular vesicle GATA2 mRNA analysis improves the detection of high risk prostate cancer and may reduce the number of unnecessary biopsies.

Keywords: GATA2 transcription factor; TMPRSS2-ERG fusion protein; extracellular vesicles; human; prostate cancer antigen 3; prostatic neoplasms.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Scheme of study design. EV= extracellular vesicle, FFPE= formalin-fixed paraffin embedded.
Fig. 2.
Fig. 2.
Analysis of EV GATA2 mRNA in A) paired pre- and post-RP urine samples (n=16, t-test); B) matching urine and RP FFPE tissue (n=19, Pearson correlation); C) biopsy-negative and -positive (t-test); D) low- versus high-grade PCa (t-test); E) pT2 compared to pT3 (t-test) and; F) PSA<4ng/ml comparted to PSA≥4ng (t-test) in the training and validation cohorts. EV = extracellular vesicle; BxN = biopsy negative; PCa = prostate cancer; GS = Gleason score; pT = pathological stages RP = radical prostatectomy; FFPE = formalin-fixed paraffin-embedded.
Fig. 3.
Fig. 3.
Receiver operating characteristic (ROC) curves show the performance of individual genes, SOC, PT-E, GAPT-E and GAPT-E plus SOC in discriminating any cancer (A and B) and high-grade disease (C and D) in the training (n=48) and validation (n=146) cohorts. SOC = standard of care. PT-E= PCA3, and TMPRSS2-ERG. GAPT-E= GATA2, PCA3, and TMPRSS2-ERG.
Fig. 4.
Fig. 4.
Waterfall plot of A) GAPT-E and B) PT-E scores in relation to biopsy outcomes across the validation cohort (n=146). Dashed line is high-grade cutoff and solid line is cutoff for any cancer. For the PT-E test the high-grade and any cancer cutoffs are the same, hence the lines are coincident. Each colored bar represents an individual patient’s score, increasing from left to right. Blue, biopsy negative; Yellow, GS≤6; and Red, GS≥7. GAPT-E = GATA2, PCA3, and TMPRSS2-ERG; PT-E= PCA3, and TMPRSS2-ERG.
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Comment in

  • Editorial Comment.
    Helfand BT, Glaser AP. Helfand BT, et al. J Urol. 2020 Oct;204(4):700. doi: 10.1097/JU.0000000000001066.01. Epub 2020 Jul 30. J Urol. 2020. PMID: 32898984 No abstract available.

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