Supplementary Material for: Cyclin A2 expression as predictive biomarker in muscle-invasive upper tract urothelial carcinoma

Introduction: The aim was to evaluate the prognostic value of altered Cyclin A2 (CCNA2) gene expression in upper tract urothelial carcinoma (UTUC) and to assess its predictive potential as prognostic factor for overall survival (OS) and disease-free survival (DFS).
Methods: 62 patients who underwent surgical treatment for UTUC were included. Gene expression of CCNA2, MKI67 and p53 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 CCNA2 expression with MKI67 and p53.
Results: 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 CCNA2 expression levels showed longer OS (HR 0.33; 95% CI 0.15 - 0.74; p = 0.0073). Multivariable Cox regression analyses identified CCNA2 overexpression (HR 0.37; 95% CI 0.16 - 0.85; p = 0.0189) and grading G2 (vs. G3) (HR 0.39; 95% CI 0.17 - 0.87; p = 0.0168) to be independent predictors for longer OS. CCNA2 expression correlated positively with MKI67 expression (Rho = 0.4376, p = 0.0005).
Conclusion: Low CCNA2 expression is significantly associated with worse OS. Thus, CCNA2 might serve as 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.

引言：本研究旨在评估细胞周期蛋白A2（Cyclin A2, CCNA2）基因表达异常在上尿路尿路上皮癌（upper tract urothelial carcinoma, UTUC）中的预后价值，并评估其作为总生存期（overall survival, OS）和无病生存期（disease-free survival, DFS）预后因子的预测潜力。方法：纳入62例接受上尿路尿路上皮癌手术治疗的患者。采用定量逆转录聚合酶链反应分析CCNA2、MKI67及p53的基因表达。生存分析采用Kaplan-Meier法及对数秩检验（log-rank test）。Cox回归分析中，计算单变量及多变量风险比。采用Spearman相关分析探讨CCNA2表达与MKI67、p53的相关性。结果：本队列患者的中位年龄为73岁，其中男性48例（占比77.4%），女性14例（占比22.6%）。CCNA2高表达患者的总生存期更长（风险比HR=0.33，95%置信区间CI：0.15~0.74，P=0.0073）。多变量Cox回归分析显示，CCNA2过表达（HR=0.37，95%CI：0.16~0.85，P=0.0189）及G2级肿瘤（相较于G3级，HR=0.39，95%CI：0.17~0.87，P=0.0168）为总生存期延长的独立预测因素。CCNA2表达与MKI67表达呈正相关（Rho=0.4376，P=0.0005）。结论：CCNA2低表达与较差的总生存期显著相关。据此，CCNA2可作为肌层浸润性上尿路尿路上皮癌的潜在生物标志物，用于甄别预后不良的患者亚群，并可应用于未来的风险评估评分体系。