The association between PI3K, JAK/STAT pathways with the PDL-1 expression in prostate cancer

Abstract

Programmed cell death protein-1/programmed death-ligand-1 (PD-1/PDL-1) signalling pathway has gained attention in prostate cancer. The relationship between pSTAT-1, pSTAT-3 expressions and PTEN loss with PDL-1 expression was assessed and the effects of the pathways on prostate cancer prognosis were evaluated. Patients who underwent radical prostatectomy between 2011 and 2017 were included in our study. Prostatectomy materials were evaluated using immunohistochemical staining of pSTAT-1, pSTAT-3, PTEN, and PDL-1. The relationship between PDL-1 and pSTAT-1, pSTAT-3 expressions and PTEN loss was evaluated. Additionally, factors affecting biochemical recurrence-free survival and clinical progression-free survival were analysed. Within100 patients, 9 of 11 patients with PDL-1 expression also had intermediate-high pSTAT-1 staining intensity, and those with PDL-1 expression had higher pSTAT-1 staining intensity than those without (81.9% vs. 56.2%, p = 0.014). In univariate analysis, pSTAT-1, pSTAT-3 and PDL-1 expressions had significant impact on biochemical recurrence-free and clinical progression-free survival. In multivariate analysis, pSTAT-1 staining intensity with radical prostatectomy ISUP grade in terms of biochemical recurrence-free survival and the pSTAT-1 H-score with radical prostatectomy ISUP grade in terms of clinical progression-free survival were independent risk factors. Moderate-high expression of pSTAT-1 was closely associated with PDL-1 expression, and pSTAT-1 was also a predictor of biochemical recurrence and clinical progression.