Validation of a 10-gene molecular signature for predicting biochemical recurrence and clinical metastasis in localized prostate cancer
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To validate a previously characterized 10-gene signature in prostate cancer with implication to distinguish aggressive and indolent disease within low and intermediate patients’ risk groups.
A case–control study design used to select 545 patients from the Mayo clinic tumor registry who underwent radical prostatectomy. A training set from this cohort (n = 359) was used to build a 10-gene model, based on high-dimensional discriminant analysis (HDDA10) to predict several endpoints of clinical patients’ outcome. An independent set (n = 219) from the same institution was used as validation set.
HDDA10 showed significant performance for predicting metastasis (Mets) (AUC 0.68, p = 6.4E – 6) and biochemical recurrence (BCR) (AUC = 0.65, p = 0.003) in the validation set outperforming Gleason grade grouping (GG) for BCR (AUC 0.57, p = 0.03) and with comparable performance for Mets endpoint (GG AUC 0.66, p = 8.1E – 5). HDDA10 prognostic significance was superior to any clinical–pathological parameter within GG2 + 3 (GS7) patients achieving an AUC of 0.74 (p = 0.0037) for BCR compared to Gleason pattern 4 (AUC 0.64) (p = 0.015) and AUC for Mets of 0.68 versus AUC of 0.65 for Gleason pattern 4 (p = 0.01). HDDA10 remained significant for both BCR and Mets in multivariate analysis, suggesting that it can be used to increase accuracy in stratifying patients eligible for active surveillance.
HDDA10 is of added value to GG and other clinical–pathological parameters in predicting BCR and Mets endpoint, especially in the low to intermediate patients’ risk groups. HDDA10 prognostic value should be further validated prospectively in stratifying patients specifically in low to intermediate GS (GG1-2), such as active surveillance programs.
KeywordsGenetic classifier Grade grouping Gleason score Biomarkers Biochemical recurrence Clinical metastasis Prostate cancer Prognosis
This work was supported in part by the Prostate Cancer Foundation Young Investigator Award (T.A.B). This work was also supported by Prostate cancer Canada and is proudly funded by the Movember Foundation-Grant #B2013-01. This work was also supported in part by the GAP1 Movember Tissue Biomarker Project.
HAO drafted the paper, MA carried out bioinformatics and computational analysis, TAB is responsible for outline, study design and supervision of work, all authors have approved the submitted and published versions.
Compliance with ethical standards
Conflict of interest
All authors declare no conflict of interest in regards to this manuscript.
This research was performed in compliance with all ethical standards and approved by the U Calgary ethics board.
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