Sasaki Daichi, Yoneyama Tohru, Yoneyama Fumiya, Ozaki Kai, Ozaki Yusuke, Miura Yuki, Fujita Naoki, Okamoto Teppei, Yamamoto Hayato, Goto Shintaro, Yoshizawa Tadashi, Kurose Akira, Kijima Hiroshi, Ohyama Chikara, Hatakeyama Shingo
Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Department of Glycotechnology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Int J Urol. 2025 Sep;32(9):1195-1202. doi: 10.1111/iju.70122. Epub 2025 May 23.
Programmed cell death ligand 1 (PD-L1) expression is considered a poor prognostic factor in patients with muscle-invasive bladder cancer (MIBC). However, the data regarding the change in PD-L1 expression before and after neoadjuvant chemotherapy (NAC) are limited. We aimed to investigate the longitudinal association between programmed death-ligand 1 (PD-L1) and Ki-67 expression before and after NAC in muscle-invasive bladder cancer (MIBC).
We retrospectively analyzed 191 patients with MIBC who underwent platinum-based NAC followed by radical cystectomy (RC) between June 2010 and March 2022. We excluded ypT0-1 cases because of the difficulty of evaluating PD-L1 and Ki-67 by immunostaining. Finally, we selected 104 patients with matched specimens from transurethral resection of bladder tumor (TURBT) and residual invasive disease in RC. We examined the relationship between PD-L1 expression and Ki-67 labeling index in TURBT and RC specimens. Additionally, we investigated the differential expression of 39 subtype-related genes before and after NAC.
Among 104 patients who underwent NAC, the number of PD-L1-positive patients significantly increased from 16 (15.4%) in the TURBT specimens to 30 (28.8%) in the RC specimens. The median Ki-67 labeling index significantly decreased from 30.6% in the TURBT specimens to 9.9% in the RC specimens. The correlation between treatment effects and changes in gene expression was challenging to identify.
A significant effect of NAC on PD-L1 expression and Ki-67 labeling index was observed in patients with MIBC. However, the impact of changes in gene expression on prognosis needs further study.
程序性细胞死亡配体1（PD-L1）表达被认为是肌肉浸润性膀胱癌（MIBC）患者的不良预后因素。然而，关于新辅助化疗（NAC）前后PD-L1表达变化的数据有限。我们旨在研究肌肉浸润性膀胱癌（MIBC）患者在NAC前后程序性死亡配体1（PD-L1）与Ki-67表达之间的纵向关联。
我们回顾性分析了2010年6月至2022年3月期间接受铂类NAC并随后行根治性膀胱切除术（RC）的191例MIBC患者。由于通过免疫染色评估PD-L1和Ki-67存在困难，我们排除了ypT0-1病例。最后，我们选择了104例经尿道膀胱肿瘤切除术（TURBT）和RC中残余浸润性疾病的匹配标本患者。我们检查了TURBT和RC标本中PD-L1表达与Ki-67标记指数之间的关系。此外，我们研究了NAC前后39个亚型相关基因的差异表达。
在104例接受NAC的患者中，PD-L1阳性患者的数量从TURBT标本中的16例（15.4%）显著增加至RC标本中的30例（28.8%）。Ki-67标记指数的中位数从TURBT标本中的30.6%显著降至RC标本中的9.9%。治疗效果与基因表达变化之间的相关性难以确定。
在MIBC患者中观察到NAC对PD-L1表达和Ki-67标记指数有显著影响。然而，基因表达变化对预后的影响需要进一步研究。
