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.
Molecular oncology. 2016 Oct 19 [Epub]
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
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA., Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Illumina, Inc., San Diego, CA, USA., Departments of Pathology and Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA., Department of Urology, Eastern Virginia Medical School, Norfolk, VA, USA., Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA., Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.