Department of Urology, University Hospital, Tübingen, Germany.
Cardiovascular Center, Oberallgäu-Kempten, Kempten, Germany.
Eur Urol Focus. 2022 May;8(3):718-727. doi: 10.1016/j.euf.2021.04.015. Epub 2021 May 4.
Receptor activator of NF kappa B (RANK) and its ligand have an essential role in T-cell regulation and the development of bone metastases. The role of RANK expression in muscle-invasive bladder cancer (MIBC) is unknown.
To assess the relevance of RANK expression in patients with MIBC.
DESIGN, SETTING, AND PARTICIPANTS: Expression of RANK was assessed via immunohistochemistry of benign urothelium, MIBC tissue, and lymph node metastases from 153 patients undergoing radical cystectomy. Expression data from The Cancer Genome Atlas (TCGA) cohort were analyzed for potential associations with molecular subtypes and outcome.
RANK expression was correlated with clinical and pathological parameters and to individual data for the clinical course of MIBC.
Expression of RANK was significantly higher in both primary tumors (p = 0.02) and lymph node metastases (p = 0.01) compared to normal urothelium. In tumor tissue, RANK expression was significantly lower in patients with locally advanced disease and lymph node involvement compared to those with organ-confined disease (p = 0.0009) and node-negative MIBC (p = 0.0002). In univariable and multivariable analyses, high expression of RANK was associated with a longer time to recurrence (p = 0.0005 and 0.01) and better cancer-specific (p = 0.0004 and 0.007) and overall survival (p = 0.002 and 0.04). High expression of RANK was associated with better outcome for patients with luminal infiltrated tumors in the TCGA cohort.
RANK expression is increased in bladder cancer tissue compared to benign urothelium, with higher expression in organ-defined compared to locally advanced disease. High RANK expression indicates a favorable prognosis in MIBC. The prognostic role differs in tumors of different molecular subtypes.
Expression of a protein involved in bone turnover regulation (RANK) is higher in bladder cancer tissue than in benign bladder tissue. However, high levels of RANK on tumor cells indicate favorable prognosis for patients with bladder cancer that invades the muscle layer of the bladder.
核因子-κB 受体激活物（RANK）及其配体在 T 细胞调节和骨转移的发展中具有重要作用。RANK 表达在肌肉浸润性膀胱癌（MIBC）中的作用尚不清楚。
评估 RANK 表达在 MIBC 患者中的相关性。
设计、设置和参与者：对 153 例接受根治性膀胱切除术的患者的良性尿路上皮、MIBC 组织和淋巴结转移进行免疫组织化学检测，以评估 RANK 表达。对癌症基因组图谱（TCGA）队列的表达数据进行分析，以确定与分子亚型和结果的潜在关联。
RANK 表达与临床和病理参数相关，并与 MIBC 个体数据的临床病程相关。
与正常尿路上皮相比，原发肿瘤（p=0.02）和淋巴结转移（p=0.01）中的 RANK 表达均显著升高。在肿瘤组织中，与局限于器官的疾病和淋巴结受累的患者相比，局部进展性疾病和淋巴结受累的患者 RANK 表达明显降低（p=0.0009 和 p=0.0002）。在单变量和多变量分析中，RANK 高表达与复发时间延长相关（p=0.0005 和 0.01），癌症特异性生存（p=0.0004 和 0.007）和总生存（p=0.002 和 0.04）更好。在 TCGA 队列中，RANK 高表达与 luminal 浸润性肿瘤患者的预后更好相关。
与良性尿路上皮相比，膀胱癌组织中 RANK 表达增加，与局限性疾病相比，器官定义性疾病中 RANK 表达更高。RANK 高表达提示 MIBC 预后良好。在不同分子亚型的肿瘤中，预后作用不同。
参与骨代谢调节的蛋白（RANK）在膀胱癌组织中的表达高于良性膀胱组织。然而，肿瘤细胞上高水平的 RANK 表明膀胱癌侵犯膀胱肌肉层的患者预后较好。
