ProstaTrend-A Multivariable Prognostic RNA Expression Score for Aggressive Prostate Cancer.
Biomarker
Molecular diagnostic testing
Molecular pathology
Next-generation sequencing
Personalized medicine
Prostate cancer
Transcriptome
Journal
European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
12
11
2019
accepted:
02
06
2020
pubmed:
8
7
2020
medline:
16
7
2021
entrez:
8
7
2020
Statut:
ppublish
Résumé
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. To develop an RNA expression-based score for the prediction of PCa prognosis that facilitates clinical decision making. 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. 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). 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) ≥3 and resection status (p=0.001; DoD, training cohort) and for GG≥3, pathological stage ≥T3, and resection state (p=0.037; BCR, validation cohort). ProstaTrend is a transcriptome-based score that predicts DoD and BCR in cohorts of PCa patients treated with RP. ProstaTrend provides molecular patient risk stratification after radical prostatectomy.
Sections du résumé
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) ≥3 and resection status (p=0.001; DoD, training cohort) and for GG≥3, pathological stage ≥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.
Identifiants
pubmed: 32631745
pii: S0302-2838(20)30428-0
doi: 10.1016/j.eururo.2020.06.001
pii:
doi:
Substances chimiques
RNA, Neoplasm
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
452-459Informations de copyright
Copyright © 2020. Published by Elsevier B.V.