Gene expression panel predicts metastatic-lethal prostate cancer outcomes in men diagnosed with clinically localized prostate cancer

Rohina Rubicz, Shanshan Zhao, Jonathan L. Wright, Ilsa Coleman, Catherine Grasso, Milan S. Geybels, Amy Leonardson, Suzanne Kolb, Craig April, Marina Bibikova, Dean Troyer, Raymond Lance, Daniel W. Lin, Elaine A. Ostrander, Peter S. Nelson, Jian Bing Fan, Ziding Feng, Janet L. Stanford

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Prognostic biomarkers are needed to distinguish patients with clinically localized prostate cancer (PCa) who are at high risk of metastatic progression. The tumor transcriptome may reveal its aggressiveness potential and have utility for predicting adverse patient outcomes. Genomewide gene expression levels were measured in primary tumor samples of 383 patients in a population-based discovery cohort, and from an independent clinical validation dataset of 78 patients. Patients were followed for ≥ 5 years after radical prostatectomy to ascertain outcomes. Area under the receiver-operating characteristic curve (AUC), partial AUC (pAUC, 95% specificity), and P-value criteria were used to detect and validate the differentially expressed transcripts. Twenty-three differentially expressed transcripts in patients with metastatic-lethal compared with nonrecurrent PCa were validated (P < 0.05; false discovery rate < 0.20) in the independent dataset. The addition of each validated transcript to a model with Gleason score showed that 17 transcripts significantly improved the AUC (range: 0.83-0.88; all P-values < 0.05). These differentially expressed mRNAs represent genes with diverse cellular functions related to tumor aggressiveness. This study validated 23 gene transcripts for predicting metastatic-lethal PCa in patients surgically treated for clinically localized disease. Several of these mRNA biomarkers have clinical potential for identifying the subset of PCa patients with more aggressive tumors who would benefit from closer monitoring and adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)140-150
Number of pages11
JournalMolecular oncology
Volume11
Issue number2
DOIs
StatePublished - Feb 2017
Externally publishedYes

Keywords

  • Biomarkers
  • Gene expression
  • Metastasis
  • Prognosis
  • Prostate cancer
  • Validation

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Genetics
  • Cancer Research

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