Hao G Nguyen1, Christopher Welty1, Karla Lindquist1, Vy Ngo1, Elizabeth Gilbert1, Henrik Bengtsson2, Cristina Magi-Galluzzi3, Jerome Jean-Gilles4, Jorge Yao4, Matthew Cooperberg1, Edward Messing5, Eric A Klein6, Peter R Carroll1, Pamela L Paris7. 1. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California. 2. Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California. 3. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio. 4. Department of Pathology, University of Rochester, Rochester, New York. 5. Department of Urology, University of Rochester, Rochester, New York. 6. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. 7. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California. Electronic address: Pamela.Paris@ucsf.edu.
Abstract
PURPOSE: We aimed to validate GEMCaP (Genomic Evaluators of Metastatic Cancer of the Prostate) as a novel copy number signature predictive of prostate cancer recurrence. MATERIALS AND METHODS: We randomly selected patients who underwent radical prostatectomy at Cleveland Clinic or University of Rochester from 2000 to 2005. DNA isolated from the cancer region was extracted and subjected to high resolution array comparative genomic hybridization. A high GEMCaP score was defined as 20% or greater of genomic loci showing copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and the risk of biochemical recurrence. RESULTS: We report results in 140 patients. Overall 38% of patients experienced recurrence with a median time to recurrence of 45 months. Based on the CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical) score 39% of the patients were at low risk, 42% were at intermediate risk and 19% were at high risk. The GEMCaP score was high (20% or greater) in 31% of the cohort. A high GEMCaP score was associated with a higher risk of biochemical recurrence (HR 2.69, 95% CI 1.51-4.77) and it remained associated after adjusting for CAPRA-S score and age (HR 1.94, 95% CI 1.06-3.56). The C-index of GEMCaP alone was 0.64, which improved when combined with the CAPRA-S score and patient age (C-index = 0.75). CONCLUSIONS: A high GEMCaP score was associated with biochemical recurrence in 2 external cohorts. This remained true after adjusting for clinical and pathological factors. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify patients with prostate cancer for early adjuvant therapy.
PURPOSE: We aimed to validate GEMCaP (Genomic Evaluators of Metastatic Cancer of the Prostate) as a novel copy number signature predictive of prostate cancer recurrence. MATERIALS AND METHODS: We randomly selected patients who underwent radical prostatectomy at Cleveland Clinic or University of Rochester from 2000 to 2005. DNA isolated from the cancer region was extracted and subjected to high resolution array comparative genomic hybridization. A high GEMCaP score was defined as 20% or greater of genomic loci showing copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and the risk of biochemical recurrence. RESULTS: We report results in 140 patients. Overall 38% of patients experienced recurrence with a median time to recurrence of 45 months. Based on the CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical) score 39% of the patients were at low risk, 42% were at intermediate risk and 19% were at high risk. The GEMCaP score was high (20% or greater) in 31% of the cohort. A high GEMCaP score was associated with a higher risk of biochemical recurrence (HR 2.69, 95% CI 1.51-4.77) and it remained associated after adjusting for CAPRA-S score and age (HR 1.94, 95% CI 1.06-3.56). The C-index of GEMCaP alone was 0.64, which improved when combined with the CAPRA-S score and patient age (C-index = 0.75). CONCLUSIONS: A high GEMCaP score was associated with biochemical recurrence in 2 external cohorts. This remained true after adjusting for clinical and pathological factors. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify patients with prostate cancer for early adjuvant therapy.
Authors: Yalei Chen; Sudha M Sadasivan; Ruicong She; Indrani Datta; Kanika Taneja; Dhananjay Chitale; Nilesh Gupta; Melissa B Davis; Lisa A Newman; Craig G Rogers; Pamela L Paris; Jia Li; Benjamin A Rybicki; Albert M Levin Journal: BMC Med Genomics Date: 2020-08-20 Impact factor: 3.063