Horiguchi Hirotaka, Hatakeyama Shingo, Yoneyama Tohru, Yoneyama Mihoko Sutoh, Tanaka Toshikazu, Fujita Naoki, Okamoto Teppei, Yamamoto Hayato, Yoneyama Takahiro, Yoshizawa Tadashi, Hashimoto Yasuhiro, Kawaguchi Toshiaki, Ohyama Chikara
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Department of Advanced Blood Purification Therapy, Hirosaki University, Graduate School of Medicine, Hirosaki, Japan.
Urol Oncol. 2021 Apr;39(4):238.e9-238.e17. doi: 10.1016/j.urolonc.2020.11.029. Epub 2020 Dec 8.
To investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.
We retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.
The median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3-4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.
A significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.
探讨根治性膀胱切除术(RC)后肌肉浸润性膀胱癌(MIBC)患者中Ki67指数与程序性死亡配体1(PD-L1)表达之间的关联。
我们回顾性评估了2004年4月至2020年4月期间接受RC治疗的262例MIBC患者。通过单因素Cox回归分析评估Ki67指数和PD-L1表达对预后的影响。此外,构建了一个包括Ki67和PD-L1的病理分子风险评分来预测预后和病理因素。我们还在T24和5637膀胱癌细胞系中评估了白细胞介素-6刺激下Ki67指数与PD-L1之间的联系。
中位年龄和随访时间分别为69岁和52个月。Ki67指数和PD-L1表达与肿瘤复发显著相关。单因素Cox回归分析显示,pT3-4、混合组织学类型、淋巴管浸润阳性(LVI+)、pN+、Ki67高表达(>17%)和PD-L1阳性与无复发生存期(RFS)显著相关。病理分子风险评分是根据手术切缘阳性(1分)、混合组织学类型(1分)、LVI+(1分)、pN+(1分)和Ki67高表达(1分)构建的。病理分子风险评分较高(>1)的患者的RFS和总生存期明显短于风险评分较低(≤1)的患者。在白细胞介素-6刺激下,T24和5637细胞中的细胞增殖显著增加,而PD-L1表达未增加。
在MIBC患者中观察到Ki67高表达和PD-L1表达对不良预后有显著影响。有必要进一步研究以阐明MIBC患者细胞增殖和PD-L1表达的确切机制。