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

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.Electronic supplementary materialThe online version of this article (10.1186/s12894-018-0414-8) contains supplementary material, which is available to authorized users.

Relapse-Free Survival and PD-L1 Expression in First High- and Low-Grade Relapsed Luminal, Basal and Double-Negative P53-Mutant Non-Muscular Invasive Bladder Cancer Depending on Previous Chemo- and Immunotherapy

“…Different studies have been initiated to explore difficult and ambiguous relationship among a broad range of biological, social, gender and other factors involved in development, progression and treatment response of non-muscular invasive bladder cancer [1,2,[4][5][6][7][8][9][10][11]. Tumor behavior is supposed to be a result of the neoplasia's nature, its molecular subtype and malignant potential, which in sophisticated combinations increase predictive uncertainty and leave practitioners without strong prognosticators.…”

“…At the same time, some investigators reported that bladder cancer expressing high PD-L1 showed a poor prognosis [7][8][9], but others suggested high PD-L1 level predicted the good prognosis [10]. Thus, according to Kawahara et al (2018), correlation between PD-L1 expression and the prognosis remains controversial [11]. The aim of this study was to assess how PD-L1 expression in tissue specimens of patients with main molecular subtypes of NMIBC (luminal, basal and double-negative p53-mutant) associates with relapsed-free survival in dependence on the tumor grade and prior treatment of primary bladder cancer.…”

Identification of Prognostic Immune Genes in Bladder Urothelial Carcinoma

“…STAT1 and NFATC1 are considered upstream and downstream of PD-L1, respectively. Also, the expression of NFATC1 and STAT1 are associated with PD-L1 in bladder urothelial carcinoma [19]. Among other transcription factors, EBF1 has been reported in a variety of tumors and immune-related diseases [20][21][22].…”

Integrated Analysis Identifies and Validates a Novel Signature Based on Immune Related Gene Predicting Survival in Bladder Urothelial Carcinoma

“…Many studies suggested that PD-L1 and PD-1 expression could be proposed as a prognostic marker for bladder cancer [11,18]. High expression level of PD-L1 was more likely to be considered as advanced stage, higher grade, higher frequencies of recurrence and unfavorable prognosis [19][20][21].…”

“…The activated histiocytic components of TME will surely affect cell transcription suggesting a clinical value for immunotherapy of bladder cancer [27][28][29]. Therefore, the expression level of PD-L1, PD-1 and CTLA-4 might be used for measuring the different TME patterns with diverse immunohistochemistry status [18].…”