Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality

• Type of Material: Article
• Authors: Kathryn L. Pellegrini, Emory University; Martin Sanda, Emory University; Dattatraya Patil, Emory University; Qi Long, Emory University; Maria Santiago-Jimenez, GenomeDx Biosciences; Mandeep Takhar, GenomeDx Biosciences; Nicholas Erho, GenomeDx Biosciences; Kasra Yousefi, GenomeDx Biosciences; Elai Davicioni, GenomeDx Biosciences; Eric A. Klein, Cleveland Clinic; Robert B. Jenkins, Mayo Clinic; R. Jeffery Karnes, Mayo Clinic; Carlos S Moreno, Emory University
• Language: English
• Date: 2017-06-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 BJU International Published by John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/bju.13779
• Title of Journal or Parent Work: BJU International
• ISSN: 1464-4096
• Volume: 119
• Issue: 6
• Start Page: 961
• End Page: 967
• Grant/Funding Information: This research was supported by DOD grant W81XWH-010-1-0090 to CSM, NIH grants R03CA173770, R03CA183006, and R21NS091630 to QL, NIH U01CA113913 to MGS, NCI Cancer Support Center Grant P30CA138292, and travel funding from GenomeDx to RJK.
• Keywords: metastasis; Science & Technology; PREDICTION MODELS; RADICAL PROSTATECTOMY; PROGRESSION; #PCSM; ADVERSE PATHOLOGY; DISEASE; THERAPY; RECURRENCE; #ProstateCancer; Life Sciences & Biomedicine; TREATMENT DECISIONS; biomarker; RISK; GENOMIC CLASSIFIER; Urology & Nephrology
• Research Categories: Biology, Bioinformatics; Health Sciences, Oncology; Health Sciences, Pathology

Abstract

Objectives: To determine the prognostic potential of a 24-gene signature, Sig24, for identifying patients with prostate cancer who are at risk of developing metastases or of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP). Patients and Methods: Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time-dependent c-index analysis, Cox proportional hazards regression and Kaplan–Meier survival analysis. Results: Higher Sig24 scores were significantly associated with higher pathological Gleason scores in all three cohorts. Analysis of the Mayo Clinic II cohort, which included time-to-event information, indicated that patients with high Sig24 scores also had a higher risk of developing metastasis (hazard ratio [HR] 3.78, 95% confidence interval [CI]: 1.96–7.29; P < 0.001) or of PCSM (HR 6.54, 95% CI: 2.16–19.83; P < 0.001). Conclusions: The findings of the present study show the applicability of Sig24 for the prognosis of metastasis or PCSM after RP. Future studies investigating the combination of Sig24 with available prognostic tests may provide new approaches to improve risk stratification for patients with prostate cancer.