BACKGROUND: Prostate cancer (PCa) is the most prevalent solid cancer among men in Western Countries. The clinical behavior of localized PCa is highly variable. Some cancers are aggressive leading to death, while others can even be monitored safely. Hence, there is a high clinical need for precise biomarkers for identification of aggressive disease in addition to established clinical parameters. OBJECTIVE: To develop an RNA expression-based score for the prediction of PCa prognosis that facilitates clinical decision making. DESIGN, SETTING, AND PARTICIPANTS: We assessed 233 tissue specimens of PCa patients with long-term follow-up data from fr…(more)
%0 Journal Article
%1 Kreuz2020-vl
%A Kreuz, Markus
%A Otto, Dominik J
%A Fuessel, Susanne
%A Blumert, Conny
%A Bertram, Catharina
%A Bartsch, Sophie
%A Loeffler, Dennis
%A Puppel, Sven-Holger
%A Rade, Michael
%A Buschmann, Tilo
%A Christ, Sabina
%A Erdmann, Kati
%A Friedrich, Maik
%A Froehner, Michael
%A Muders, Michael H
%A Schreiber, Stephan
%A Specht, Michael
%A Toma, Marieta I
%A Benigni, Fabio
%A Freschi, Massimo
%A Gandaglia, Giorgio
%A Briganti, Alberto
%A Baretton, Gustavo B
%A Loeffler, Markus
%A Hackermüller, Jörg
%A Reiche, Kristin
%A Wirth, Manfred
%A Horn, Friedemann
%D 2020
%I Elsevier BV
%J Eur. Urol.
%K Biomarker; Molecular Next-generation Personalized Prostate Transcriptome cancer; diagnostic medicine; pathology; sequencing; testing;
%N 3
%P 452--459
%T ProstaTrend-A multivariable prognostic RNA expression score for aggressive prostate cancer
%V 78
%X BACKGROUND: Prostate cancer (PCa) is the most prevalent solid cancer among men in Western Countries. The clinical behavior of localized PCa is highly variable. Some cancers are aggressive leading to death, while others can even be monitored safely. Hence, there is a high clinical need for precise biomarkers for identification of aggressive disease in addition to established clinical parameters. OBJECTIVE: To develop an RNA expression-based score for the prediction of PCa prognosis that facilitates clinical decision making. DESIGN, SETTING, AND PARTICIPANTS: We assessed 233 tissue specimens of PCa patients with long-term follow-up data from fresh-frozen radical prostatectomies (RPs), from formalin-fixed and paraffin-embedded RP specimens and biopsies by transcriptome-wide next-generation sequencing and customized expression microarrays. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied Cox proportional hazard models to the cohorts from different platforms and specimen types. Evidence from these models was combined by fixed-effect meta-analysis to identify genes predictive of the time to death of disease (DoD). Genes were combined by a weighted median approach into a prognostic score called ProstaTrend and transferred for the prediction of biochemical recurrence (BCR) after RP in an independent cohort of The Cancer Genome Atlas (TCGA). RESULTS AND LIMITATIONS: ProstaTrend comprising ∼1400 genes was significantly associated with DoD in the training cohort of PCa patients treated by RP (leave-one-out cross-validation, Cox regression: p=2e-09) and with BCR in the TCGA validation cohort (Cox regression: p=3e-06). The prognostic impact persisted after multivariable Cox regression analysis adjusting for Gleason grading group (GG) $\geq$3 and resection status (p=0.001; DoD, training cohort) and for GG$\geq$3, pathological stage $\geq$T3, and resection state (p=0.037; BCR, validation cohort). CONCLUSIONS: ProstaTrend is a transcriptome-based score that predicts DoD and BCR in cohorts of PCa patients treated with RP. PATIENT SUMMARY: ProstaTrend provides molecular patient risk stratification after radical prostatectomy.
@article{Kreuz2020-vl,
abstract = {BACKGROUND: Prostate cancer (PCa) is the most prevalent solid cancer among men in Western Countries. The clinical behavior of localized PCa is highly variable. Some cancers are aggressive leading to death, while others can even be monitored safely. Hence, there is a high clinical need for precise biomarkers for identification of aggressive disease in addition to established clinical parameters. OBJECTIVE: To develop an RNA expression-based score for the prediction of PCa prognosis that facilitates clinical decision making. DESIGN, SETTING, AND PARTICIPANTS: We assessed 233 tissue specimens of PCa patients with long-term follow-up data from fresh-frozen radical prostatectomies (RPs), from formalin-fixed and paraffin-embedded RP specimens and biopsies by transcriptome-wide next-generation sequencing and customized expression microarrays. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied Cox proportional hazard models to the cohorts from different platforms and specimen types. Evidence from these models was combined by fixed-effect meta-analysis to identify genes predictive of the time to death of disease (DoD). Genes were combined by a weighted median approach into a prognostic score called ProstaTrend and transferred for the prediction of biochemical recurrence (BCR) after RP in an independent cohort of The Cancer Genome Atlas (TCGA). RESULTS AND LIMITATIONS: ProstaTrend comprising ∼1400 genes was significantly associated with DoD in the training cohort of PCa patients treated by RP (leave-one-out cross-validation, Cox regression: p=2e-09) and with BCR in the TCGA validation cohort (Cox regression: p=3e-06). The prognostic impact persisted after multivariable Cox regression analysis adjusting for Gleason grading group (GG) $\geq$3 and resection status (p=0.001; DoD, training cohort) and for GG$\geq$3, pathological stage $\geq$T3, and resection state (p=0.037; BCR, validation cohort). CONCLUSIONS: ProstaTrend is a transcriptome-based score that predicts DoD and BCR in cohorts of PCa patients treated with RP. PATIENT SUMMARY: ProstaTrend provides molecular patient risk stratification after radical prostatectomy.},
added-at = {2024-09-10T11:54:51.000+0200},
author = {Kreuz, Markus and Otto, Dominik J and Fuessel, Susanne and Blumert, Conny and Bertram, Catharina and Bartsch, Sophie and Loeffler, Dennis and Puppel, Sven-Holger and Rade, Michael and Buschmann, Tilo and Christ, Sabina and Erdmann, Kati and Friedrich, Maik and Froehner, Michael and Muders, Michael H and Schreiber, Stephan and Specht, Michael and Toma, Marieta I and Benigni, Fabio and Freschi, Massimo and Gandaglia, Giorgio and Briganti, Alberto and Baretton, Gustavo B and Loeffler, Markus and Hackerm{\"u}ller, J{\"o}rg and Reiche, Kristin and Wirth, Manfred and Horn, Friedemann},
biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/2c0bd4689f6aecdd4767deb073db7fdc3/scadsfct},
interhash = {fb413fbd23727ccd97c5b9f5ae2440ab},
intrahash = {c0bd4689f6aecdd4767deb073db7fdc3},
journal = {Eur. Urol.},
keywords = {Biomarker; Molecular Next-generation Personalized Prostate Transcriptome cancer; diagnostic medicine; pathology; sequencing; testing;},
language = {en},
month = sep,
number = 3,
pages = {452--459},
publisher = {Elsevier BV},
timestamp = {2024-09-10T11:54:51.000+0200},
title = {{ProstaTrend-A} multivariable prognostic {RNA} expression score for aggressive prostate cancer},
volume = 78,
year = 2020
}
