title: Gene expression panel predicts metastatic-lethal prostate cancer outcomes in men diagnosed with clinically localized prostate cancer.
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.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Rohina
authors.initials: R
authors.lastname: Rubicz
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Ilsa
authors.initials: I
authors.lastname: Coleman
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Grasso
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, The Netherlands.
authors.forename: Milan S
authors.initials: MS
authors.lastname: Geybels
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Leonardson
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.affiliation: Illumina, Inc., San Diego, CA, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: April
authors.affiliation: Illumina, Inc., San Diego, CA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.affiliation: Departments of Pathology and Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Troyer
authors.affiliation: Department of Urology, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lance
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.affiliation: Illumina, Inc., San Diego, CA, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D030561:Databases, Nucleic Acid; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: biomarkers; gene expression; metastasis; prognosis; prostate cancer; validation