Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
First Department of Urology, 'Laiko' General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Carcinogenesis. 2019 Aug 22;40(8):965-974. doi: 10.1093/carcin/bgz045.
In the era of precision oncology, bladder cancer (BlCa) is characterized by generic patient management and lack of personalized prognosis and surveillance. Herein, we have studied the clinical significance of urothelial cancer associated 1 (UCA1) lncRNA in improving patients' risk stratification and prognosis. A screening cohort of 176 BlCa patients was used for UCA1 quantification. The Hedegaard et al. (n = 476) and The Cancer Genome Atlas (TCGA) provisional (n = 413) were analyzed as validation cohorts for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. Patients' survival outcome was assessed using recurrence and progression for NMIBC or death for MIBC as clinical endpoint events. Bootstrap analysis was performed for internal validation of Cox regression analysis, whereas the clinical benefit of disease prognosis was assessed by decision curve analysis. UCA1 was significantly overexpressed in bladder tumors compared with normal urothelium, which was confirmed only in the case of NMIBC. Interestingly, reduced expression of UCA1 was correlated with muscle-invasive disease as well as with tumors of higher stage and grade. UCA1 loss was strongly associated with higher risk of short-term relapse [hazard ratio (HR) = 1.974; P = 0.032] and progression to invasive stages (HR = 3.476; P = 0.023) in NMIBC. In this regard, Hedegaard et al. and TCGA validation cohorts confirmed the unfavorable prognostic nature of UCA1 loss in BlCa. Finally, prognosis prediction models integrating UCA1 underexpression and established clinical disease markers contributed to improved stratification specificity and superior clinical benefit for NMIBC prognosis. Underexpression of UCA1 correlates with worse disease outcome in NMIBC and contributes to superior prediction of disease early relapse and progression as well as improved patient stratification specificity.
在精准肿瘤学时代，膀胱癌（BlCa）的特点是通用的患者管理，缺乏个性化的预后和监测。在此，我们研究了尿路上皮癌相关 1（UCA1）lncRNA 在改善患者风险分层和预后方面的临床意义。使用 176 例 BlCa 患者的筛选队列来定量 UCA1。Hedegaard 等人（n=476）和癌症基因组图谱（TCGA）临时队列（n=413）分别被分析为非肌肉浸润性膀胱癌（NMIBC）和肌肉浸润性膀胱癌（MIBC）的验证队列。使用 NMIBC 的复发和进展或 MIBC 的死亡作为临床终点事件来评估患者的生存结果。Cox 回归分析的内部验证采用了自举分析，而通过决策曲线分析评估了疾病预后的临床获益。与正常尿路上皮相比，UCA1 在膀胱肿瘤中显著过表达，仅在 NMIBC 中得到证实。有趣的是，UCA1 的表达降低与肌层浸润性疾病以及更高分期和分级的肿瘤相关。UCA1 的缺失与 NMIBC 中短期复发的高风险[风险比（HR）=1.974；P=0.032]和进展为侵袭性阶段（HR=3.476；P=0.023）密切相关。在这方面，Hedegaard 等人和 TCGA 验证队列证实了 UCA1 缺失在 BlCa 中的不良预后性质。最后，整合 UCA1 低表达和既定临床疾病标志物的预后预测模型有助于提高 NMIBC 预后的分层特异性和更高的临床获益。UCA1 的低表达与 NMIBC 的不良疾病结局相关，有助于更好地预测疾病早期复发和进展，并提高患者分层的特异性。
