title: Clinical and genomic analysis of metastatic prostate cancer progression with a background of postoperative biochemical recurrence.
abstract: OBJECTIVE
  To better characterize the genomics of patients with biochemical recurrence (BCR) who have metastatic disease progression in order to improve treatment decisions for prostate cancer.
  
  
  METHODS
  The expression profiles of three clinical outcome groups after radical prostatectomy (RP) were compared: those with no evidence of disease (NED; n = 108); those with BCR (rise in prostate-specific antigen [PSA] level without metastasis; n = 163); and those with metastasis (n = 192). The patients were profiled using Human Exon 1.0 ST microarrays, and outcomes were supported by a median 18 years of follow-up. A metastasis signature was defined and verified in an independent RP cohort to ensure the robustness of the signature. Furthermore, bioinformatics characterization of the signature was conducted to decipher its biology.
  
  
  RESULTS
  Minimal gene expression differences were observed between adjuvant treatment-naïve patients in the NED group and patients without metastasis in the BCR group. More than 95% of the differentially expressed genes (metastasis signature) were found in comparisons between primary tumours of metastasis patients and the two other outcome groups. The metastasis signature was validated in an independent cohort and was significantly associated with cell cycle genes, ubiquitin-mediated proteolysis, DNA repair, androgen, G-protein coupled and NOTCH signal transduction pathways.
  
  
  CONCLUSIONS
  This study shows that metastasis development after BCR is associated with a distinct transcriptional programme that can be detected in the primary tumour. Patients with NED and BCR have highly similar transcriptional profiles, suggesting that measurement of PSA on its own is a poor surrogate for lethal disease. Use of genomic testing in patients undergoing RP with an initial rise in PSA level may be useful to improve secondary therapy decision-making.
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalalfa
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Anamaria
authors.initials: A
authors.lastname: Crisan
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Ismael A
authors.initials: IA
authors.lastname: Vergara
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Ghadessi
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Buerki
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Kasra
authors.initials: K
authors.lastname: Yousefi
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sierocinski
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Haddad
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: GenomeDx Biosciences, Inc., Vancouver, BC, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
mesh_terms: D016022:Case-Control Studies; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011184:Postoperative Period; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D060066:Protein Interaction Maps / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
chemical_list: D022661:RNA, Untranslated; D017430:Prostate-Specific Antigen
keywords: biochemical recurrence; gene expression; gene functional analysis; metastasis; prostate cancer