Abstract

<div>Abstract<p><b>Purpose:</b> In this era of molecular diagnostics, prediction of clear-cell renal cell cancer (ccRCC) survival requires optimization, as current prognostic markers fail to determine individual patient outcome. Epigenetic events are promising molecular markers. Promoter CpG island methylation of <i>cysteine dioxygenase type 1</i> (<i>CDO1</i>), which was identified as prognostic marker for breast cancer, is studied as a potential marker for ccRCC survival.</p><p><b>Experimental Design:</b> We collected primary tissues of 365 ccRCC cases identified within the prospective Netherlands Cohort Study (NLCS). In this population-based series, <i>CDO1</i> promoter methylation was observed in 124 of 324 (38.3%) patients with successful methylation-specific PCR analysis. Kaplan–Meier curves and Wilcoxon tests were used to evaluate 10-year ccRCC-specific survival. Cox regression analysis was used to obtain crude and multivariate HRs and 95% confidence intervals (CI). The relative prognostic value of multivariate models with and without <i>CDO1</i> promoter methylation was compared using likelihood-ratio tests.</p><p><b>Results:</b> Patients with <i>CDO1</i> promoter methylation have a significantly poorer survival than those without (Wilcoxon <i>P</i> = 0.006). Differences in survival were independent of other prognostic factors, including age and sex (HR, 1.66; 95% CI, 1.12–2.45) and TNM stage, tumor size, and Fuhrman grade (HR, 1.89; 95% CI, 1.25–2.85). Multivariate models performed better with than without <i>CDO1</i> promoter methylation status (likelihood-ratio <i>P</i> = 0.003). Survival curves were validated in an independent series of 280 ccRCC cases from The Cancer Genome Atlas (TCGA; Wilcoxon <i>P</i> < 0.001).</p><p><b>Conclusions:</b> <i>CDO1</i> promoter methylation may not substitute common prognostic makers to predict ccRCC survival, but offers additional, relevant prognostic information, indicating that it might be a novel molecular marker to determine ccRCC prognosis. <i>Clin Cancer Res; 21(15); 3492–500. ©2015 AACR</i>.</p></div>

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