Expression and significance of programmed cell death ligand-1 in neuroblastoma tissues

Abstract

Objective: To investigate the relationship between expression of programmed cell death ligand-1(PD-L1) in the tissue of neuroblastoma (NB) and patient's clinical characteristics and prognosis. Methods: Clinical data and surgical tissue paraffin blocks of 100 newly diagnosed NB children at Sun Yat-sen University Cancer Center between January 2000 and December 2015 were collected and the expression level of PD-L1 and its' relationship with pathological parameters and survival rate were analyzed retrospectively. The ratio between groups was compared by chi-square test. Kaplan-Meier method was used for survival analysis and COX regression model was used for multivariate analysis. Results: Among 100 cases, 71 were males and 29 females; there were 5 cases of stageⅠ, 4 cases of stageⅡ, 19 cases of stage Ⅲ, 65 cases of stage Ⅳ and 7 cases of stage Ⅳs. Ten out of 62 cases (16%) were N-MYC amplified; 15 cases were in low-risk group, 18 were in medium-risk group and 67 were in high-risk group. The positive rate of PD-L1 in NB tumor tissue was 57% (57/100), of which 55 were weakly positive, 1 was moderately positive and 1 was strongly positive. The positive rates of PD-L1 expression in tumor tissues without bone metastasis were higher than those with bone metastasis(66%(39/59)vs.44%(18/41), χ(2)=4.864, P=0.027), the positive rates of PD-L1 expression in tumor tissues pathologically diagnosed as neuroblastoma were higher than those pathologically diagnosed as ganglioneuroblastoma (61%(53/87) vs.31%(4/13), χ(2)=4.195, P=0.041), the positive rates of PD-L1 expression in tumor tissues originated from abdominal cavity were higher than those originated from other places (61% (51/83)vs.35%(6/17), χ(2)=3.937,P=0.047).The 4-year event-free survival (EFS) rates of patients with PD-L1 negative and positive were 40% and 33% (χ(2)=0.009, P=0.923), respectively. The 4-year overall survival (OS) rates of patients with PD-L1 negative and positive were 62% and 58% (χ(2)=0.294, P=0.587). Among 33 non-high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 89% and 78% (χ(2)=0.001, P=0.965), the 4-year OS rates of patients with PD-L1 negative and positive were 100% and 96% (χ(2)=0.500, P=0.480). Among 67 high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 24% and 11% (χ(2)=1.154, P=0.282), the 4-year OS rates of patients with PD-L1 negative and positive were 48% and 41% (χ(2)=0.692, P=0.405). Multivariate analysis showed that N-MYC gene amplification was an independent adverse prognostic factor for OS and EFS rates of NB patients (RR: 1.726,95%CI:1.209-2.466; RR:1.326,95%CI:1.014-1.736) and advanced clinical stage was an independent adverse prognostic factor for EFS rates of NB patients (RR: 26.498, 95%CI:3.518-199.614). Conclusions: The expression of PD-L1 in NB tumor tissues was correlated with the clinical characteristics of children. However, there were no significant differences in the prognosis of patients with or without PD-L1 expression.