ObjectiveTo 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.Patients and MethodsTranscriptome‐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.ResultsIn 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).ConclusionsThis study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

中文翻译：

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基于管腔非编码 RNA 的基因组分类器证实了接受根治性膀胱切除术治疗的临床器官局限性膀胱癌患者的良好预后


目的进一步评估接受根治性膀胱切除术 （RC） 的患者队列中的基因组分类器 （GC），因为基于非编码 RNA （lncRNA） 的基因组分析表明可用于识别与膀胱癌患者预后良好的不同肿瘤亚组相对应。患者和方法使用 Decipher Bladder 对一组高级别临床器官局限 （cTa-T2N0M0） 尿路上皮癌 （UC） 患者的膀胱肿瘤样本进行经尿道切除，这些患者随后接受了 RC 而没有任何新辅助治疗 （n = 226）。使用 先前开发的 GC 确定基于 lncRNA 的管腔良好状态。主要终点是 RC 后的总生存期 （OS）。次要终点包括 RC 的癌症特异性死亡率和分期。结果在该研究中，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。我们确定了 60 例管腔有利亚型患者，所有这些患者都显示出与侵袭性较弱的膀胱癌生物学相关的稳健基因表达模式。在多变量分析中，管腔有利亚型 （vs 无） 患者与升级为病理性 （p）T3+ 疾病的较低几率显著相关 （比值比 [OR] 0.32,95% 置信区间 [CI] 0.12-0.82;P = 0.02）、任何上期 （OR 0.41,95% CI 0.20-0.83;P = 0.01）和任何分期和/或 pN+ （OR 0.50,95% CI 0.25-1.00;P = 0.05）。管腔有利的膀胱癌与较好的 OS 显著相关 （风险比 0.33,95% CI 0.15-0.74;P = 0.007）。结论本研究验证了 GC 在识别具有管腔有利亚型、肿瘤生物学侵袭性较低的 UC 方面的性能。