Cyclin A2 Expression as Predictive Biomarker in Muscle-Invasive Upper Tract Urothelial Carcinoma

Abstract

<b><i>Introduction:</i></b> The aim was to evaluate the prognostic value of altered <i>Cyclin A2 (CCNA2)</i> gene expression in upper tract urothelial carcinoma (UTUC) and to assess its predictive potential as a prognostic factor for overall survival (OS) and disease-free survival. <b><i>Methods:</i></b> 62 patients who underwent surgical treatment for UTUC were included. Gene expression of <i>CCNA2</i>, <i>MKI67</i>, and <i>p53</i> was analyzed by quantitative reverse transcriptase polymerase chain reaction. Survival analyses were performed using the Kaplan-Meier method and the log-rank test. For Cox regression analyses, uni- and multivariable hazard ratios were calculated. Spearman correlation was used to analyze correlation of <i>CCNA2</i> expression with <i>MKI67</i> and <i>p53</i>. <b><i>Results:</i></b> The median age of the cohort was 73 years, and it consisted of 48 males (77.4%) and 14 females (22.6%). Patients with high <i>CCNA2</i> expression levels showed longer OS (HR 0.33; 95% CI: 0.15–0.74; <i>p</i> = 0.0073). Multivariable Cox regression analyses identified <i>CCNA2</i> overexpression (HR 0.37; 95% CI: 0.16–0.85; <i>p</i> = 0.0189) and grading G2 (vs. G3) (HR 0.39; 95% CI: 0.17–0.87; <i>p</i> = 0.0168) to be independent predictors for longer OS. <i>CCNA2</i> expression correlated positively with <i>MKI67</i> expression (Rho = 0.4376, <i>p</i> = 0.0005). <b><i>Conclusion:</i></b> Low <i>CCNA2</i> expression is significantly associated with worse OS. Thus, <i>CCNA2</i> might serve as a potential biomarker in muscle-invasive UTUC and may be used to characterize a subset of patients having an unfavorable outcome and for future risk assessment scores.