Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Eur Urol. 2017 Jun;71(6):961-969. doi: 10.1016/j.eururo.2016.12.016. Epub 2017 Jan 6.
Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment.
To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations.
DESIGN, SETTING, AND PARTICIPANTS: Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non-muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n=216, Cx n=27) and plasma samples (NMIBC n=39, Cx n=27) from patients harbouring mutations were subsequently screened using ddPCR assays.
Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied.
In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p=0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p=0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study.
Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer.
Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays.
对膀胱癌患者进行疾病监测对于早期诊断进展和转移以及优化治疗非常重要。
开发用于 FGFR3 和 PIK3CA 肿瘤突变的疾病监测的尿液和血浆检测。
设计、设置和参与者：开发了液滴数字聚合酶链反应（ddPCR）检测，并对两个患者队列的肿瘤 DNA 进行了 FGFR3 和 PIK3CA 热点突变筛查。一个队列包括 363 例非肌肉浸润性膀胱癌（NMIBC）患者。另一个队列包括 468 例接受根治性膀胱切除术（Cx）的膀胱癌患者。随后使用 ddPCR 检测对携带突变的患者的尿液上清液（NMIBC n=216，Cx n=27）和血浆样本（NMIBC n=39，Cx n=27）进行了筛查。
测量无进展生存期、无复发生存期和总生存期。应用 Fisher 精确检验、Wilcoxon 秩和检验和 Cox 回归分析。
总共，36%的 NMIBC 患者（363 例中的 129 例）和 11%的 Cx 患者（403 例中的 44 例）携带至少一种 FGFR3 或 PIK3CA 突变。对 NMIBC 队列的连续尿液上清液 DNA 的筛查显示，高水平的肿瘤 DNA（tDNA）与 NMIBC 的晚期疾病进展相关（p=0.003）。此外，在 Cx 队列中，血浆样本中高水平的 tDNA与复发相关（p=0.016）。观察到尿液和血浆中 tDNA 水平之间存在正相关（相关系数 0.6）。该研究的局限性在于回顾性研究设计和可用于分析的血浆量低。
膀胱癌患者尿液和血浆中 FGFR3 和 PIK3CA 突变 DNA 水平升高预示着疾病进展和转移。
膀胱癌患者的尿液和血浆可能通过突变检测进行监测，以诊断进展和转移。
