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Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer
Authors:Hirotaka Horiguchi  Shingo Hatakeyama  Tohru Yoneyama  Mihoko Sutoh Yoneyama  Toshikazu Tanaka  Naoki Fujita  Teppei Okamoto  Hayato Yamamoto  Takahiro Yoneyama  Tadashi Yoshizawa  Yasuhiro Hashimoto  Toshiaki Kawaguchi  Chikara Ohyama
Institution:1. Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan;2. Department of Advanced Blood Purification Therapy, Hirosaki University, Graduate School of Medicine, Hirosaki, Japan;3. Department of Glycotechnology, Center for Advanced Medical Research;4. Department of Cancer Immunology and Cell Biology, Oyokyo Kidney Research Institute, Hirosaki, Japan;5. Department of Urology, Aomori Prefectural Central Hospital, Japan;6. Department of Advanced Transplant and Regenerative Medicine, Hirosaki University, Graduate School of Medicine, Hirosaki, Japan;7. Department of Pathology and Bioscience, Hirosaki University, Graduate School of Medicine, Hirosaki, Japan
Abstract:ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe 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.ResultsThe 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.ConclusionsA 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.
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