Kathryn L Pellegrini1,2, Martin G Sanda1,2, Dattatraya Patil1,2, Qi Long2,3,4, María Santiago-Jiménez5, Mandeep Takhar5, Nicholas Erho5, Kasra Yousefi5, Elai Davicioni5, Eric A Klein6, Robert B Jenkins7, R Jeffrey Karnes8, Carlos S Moreno2,4,9. 1. Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. 2. Winship Cancer Institute, Atlanta, GA, USA. 3. Department of Biostatistics and Epidemiology and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 4. Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA. 5. GenomeDx Biosciences, Vancouver, BC, Canada. 6. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. 7. Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA. 8. Department of Urology, Mayo Clinic, Rochester, MN, USA. 9. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
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.
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.
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