Open AccessGene expression panel predicts metastatic‐lethal prostate cancer outcomes in men diagnosed with clinically localized prostate cancer
Author(s) -
Rubicz Rohina,
Zhao Shanshan,
Wright Jonathan L.,
Coleman Ilsa,
Grasso Catherine,
Geybels Milan S.,
Leonardson Amy,
Kolb Suzanne,
April Craig,
Bibikova Marina,
Troyer Dean,
Lance Raymond,
Lin Daniel W.,
Ostrander Elaine A.,
Nelson Peter S.,
Fan JianBing,
Feng Ziding,
Stanford Janet L.
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12014
Subject(s) - prostate cancer , medicine , oncology , prostatectomy , cancer , receiver operating characteristic , population , biomarker , cohort , area under the curve , proportional hazards model , prostate , biology , biochemistry , environmental health
Prognostic biomarkers are needed to distinguish patients with clinically localized prostate cancer ( PC a) 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 PC a 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 mRNA s represent genes with diverse cellular functions related to tumor aggressiveness. This study validated 23 gene transcripts for predicting metastatic‐lethal PC a 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.