Hirotaka Horiguchi1, Shingo Hatakeyama2, Tohru Yoneyama3, Mihoko Sutoh Yoneyama4, Toshikazu Tanaka5, Naoki Fujita1, Teppei Okamoto1, Hayato Yamamoto1, Takahiro Yoneyama6, Tadashi Yoshizawa7, Yasuhiro Hashimoto1, Toshiaki Kawaguchi5, Chikara Ohyama8. 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. Electronic address: shingoh@hirosaki-u.ac.jp. 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. 8. 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; Department of Advanced Transplant and Regenerative Medicine, Hirosaki University, Graduate School of Medicine, Hirosaki, Japan.
Abstract
OBJECTIVES: To 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 METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: To 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 METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.