Expressions of programmed death-ligand 1 and 2 and phosphorylated protein kinase B in diffuse large B-cell lymphoma and their clinical significances

Abstract

Objective To investigate the expressions of programmed death-ligand 1 (PD-L1) and PD-L2 and phosphorylated protein kinase B (p-AKT) in diffuse large B-cell lymphoma (DLBCL) patients and their correlations with clinicopathological features and prognosis. Methods A total of 68 paraffin-embedded specimens of DLBCL patients diagnosed in Shanxi Provincial Cancer Hospital with detailed follow-up record from January 2010 to December 2012 were included in the study. The expressions of PD-L1, PD-L2 and p-AKT proteins in DLBCL were detected by using immunohistochemistry (IHC). Results The positive rate of PD-L1 protein in DLBCL patients was 22.1% (15/68), which was related to germinal center B-cell (GCB) subtype or not (χ2=5.591, P = 0.018), clinical stage (χ2=3.969, P = 0.046), international prognostic index (IPI) grades (χ2=4.178, P = 0.041) and treatment remission rate (χ2=6.587, P = 0.010). The positive rate of PD-L2 protein in DLBCL patients was 14.7% (10/68), which was related to extranodal metastasis or not (χ2=6.772, P = 0.009). The positive rate of p-AKT for DLBCL patients was 61.8% (42/68), which was correlated with age (≥60 years old) or not (χ2=6.227, P = 0.013), Eastern Cooperative Oncology Group (ECOG) grades (χ2=4.005, P = 0.045), B symptoms (χ2=10.187, P = 0.001) and treatment remission rate (χ2=4.096, P = 0.043). Univariate survival analysis showed that the overall survival (OS) rate and progression free survival (PFS) rate of PD-L1 protein positive expression group were lower than those of PD-L1 protein negative expression group (both P < 0.05). In the patients with non-GCB subtype, OS rate and PFS rate of PD-L1 protein positive expression group were lower than those of PD-L1 protein negative expression group (both P < 0.05). p-AKT protein positive expression group had poorer OS rate and PFS rate compared to p-AKT negative expression group (both P < 0.05). Correlation analysis showed that PD-L1 protein expression was correlated with PD-L2 and p-AKT proteins expressions (r = 0.380, P = 0.001; r = 0.273, P = 0.025). The prognosis was worse when p-AKT and PD-L1 proteins was co-expressed (P < 0.05). Multivariate analysis suggested high expressions of PD-L1 and p-AKT proteins were independent prognosis risk factors in DLBCL (both P < 0.05). Conclusions The expressions of PD-L1 and p-AKT proteins may be involved in the occurrence and development of DLBCL. Blocking PD-1 and PD-L1 access or combined blocking could provide a promising future for the clinical therapy. Key words: Lymphoma, large B-cell, diffuse; Programmed death-ligand 1; Programmed death-ligand 2; Protein kinase B; Prognosis