de Jong Joep J, Proudfoot James A, Daneshmand Siamak, Svatek Robert S, Narayan Vikram, Gibb Ewan A, Davicioni Elai, Joshi Shreyas, Dahmen Aaron, Li Roger, Inman Brant A, Shah Paras, Chaplin Iftach, Wright Jonathan, Lotan Yair
Erasmus University Medical Center, Rotterdam, The Netherlands.
Veracyte Inc., San Francisco, CA, USA.
BJU Int. 2025 Apr;135(4):648-656. doi: 10.1111/bju.16572. Epub 2024 Nov 1.
To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non-coding RNA (lncRNA)-based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer.
Transcriptome-wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy (n = 226). The lncRNA-based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer-specific mortality and upstaging at RC.
In the study, 134 patients were clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12-0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007).
This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.
在接受根治性膀胱切除术（RC）的患者队列中进一步评估一种基因组分类器（GC），因为基于长链非编码RNA（lncRNA）的基因组分析已显示其在识别与膀胱癌患者良好预后相对应的独特肿瘤亚组方面具有实用性。
对一组患有高级别、临床器官局限（cTa-T2N0M0）尿路上皮癌（UC）且随后未接受任何新辅助治疗而接受RC的患者，使用Decipher Bladder对经尿道膀胱肿瘤切除样本进行全转录组表达谱分析（n = 226）。基于lncRNA的腔面良好状态使用先前开发的GC进行确定。主要终点是RC后的总生存期（OS）。次要终点包括癌症特异性死亡率和RC时的分期上调。
在该研究中，134例患者为临床非肌层浸润性膀胱癌（cTa/Tis/T1），92例患者为cT2。我们鉴定出60例腔面良好亚型患者，所有这些患者均表现出与侵袭性较低的膀胱癌生物学相关的强大基因表达模式。多变量分析显示，腔面良好亚型患者（与无该亚型患者相比）发生病理（p）T3+疾病分期上调的几率显著较低（比值比[OR] 0.32，95%置信区间[CI] 0.12 - 0.82；P = 0.02），任何分期上调（OR 0.41，95% CI 0.20 - 0.83；P = 0.01），以及任何分期上调和/或pN+（OR 0.50，95% CI 0.25 - 1.00；P = 0.05）。腔面良好的膀胱癌与更好的OS显著相关（风险比0.33，95% CI 0.15 - 0.74；P = 0.007）。
本研究验证了GC在识别具有腔面良好亚型、肿瘤生物学侵袭性较低的UC方面的性能。
