4.4 Article

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.urolonc.2020.11.029

Keywords

Ki67; Bladder cancer; PD-L1; Cystectomy; Prognosis

Funding

  1. Japan Society for the Promotion of Science [18K09157, 19H05556, 20K09517]
  2. Grants-in-Aid for Scientific Research [18K09157, 20K09517] Funding Source: KAKEN

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The study identified a significant association between Ki67 index and PD-L1 expression with tumor recurrence in MIBC patients, which can be used as prognostic markers. The pathomolecular risk score showed strong predictive ability for tumor recurrence and overall survival in MIBC patients.
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. (C) 2020 Elsevier Inc. All rights reserved.

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