PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer

Takashi Kawahara,Koji Izumi,Yasushi Yumura,Hiroji Uemura,Masahiro Yao,Kazuhide Makiyama,Yasuhide Miyoshi,Hiroki Ito,Kimito Osaka,Narihiko Hayashi,Yusuke Ito,Kentaro Muraoka,Hisashi Hasumi,Shinji Ohtake,Yukari Ishiguro,Noboru Nakaigawa,Ikuma Kato,Jun-Ichi Teranishi,Keiichi Kondo

doi:10.1186/s12894-018-0414-8

Takashi Kawahara, Koji Izumi + Show 17 more

Open Access

https://doi.org/10.1186/s12894-018-0414-8

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Abstract

BackgroundBladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression.MethodsWe examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively.ResultsThere were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001).ConclusionsPD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.

Highlights

Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved
This study evaluated the expressions of both programed death-1 (PD-1) and PD-L1 in urothelial carcinoma and firstly examined the PD-L1 related genes: signal transducer and activator of transcription 1 (STAT1) and nuclear factor of activated T-cells (NFAT)
PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade bladder cancer PD-1 and PD-L1 were expressed in human bladder cancer tissues

Summary

Introduction

Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. Programmed death ligand 1 (PD-L1, B7-H1, CD274) is expressed in several malignancies, including bladder cancer [5,6,7]. The clinicopathological impact of this biomarker has not Recently, several clinical trials targeting PD-1/PD-L1 pathway using anti-PD-1 antibody or anti-PD-L1 antibody demonstrated the obvious benefit for the patients with urothelial cancer and were approved by Food and Drug Administration in the United States [9,10,11]. The anti-tumor effect of atezolizumab, Kawahara et al BMC Urology (2018) 18:97 the anti-PD-L1 antibody, was dependent on the PD-L1 expression status on tumor-infiltrating immune cells [9]. The correlation between PD-L1 expression and the prognosis remains controversial

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