Prognostic And Predictive Value Of Programmed Death Ligand 1(PD-L1) Expression In Gastric Cancer:A Meta-Analysis

Objective:We conducted two independent meta-analyses to further explore the prognostic role of PD-L1 in gastric cancer(Meta analysis-1)and evaluate the effect of PD-L1 expression level on anti-PD-1/PD-L1 therapy(Meta analysis-2).Methods:A literature search strategy was performed from the PubMed,Web of Science,Embase,and the Cochrane Library database as of December 1,2018.Screening according to the specified inclusion and exclusion criteria,and extracting relevant data from the final included literatures.Hazard ratio(HR)and Odds ratio(OR)along with 95%confidence:interval(95%CI)were used to evaluate the prognostic and predictive value and clinicopathofogical significance of PD-L1 expression in gastric cancer.Results:A total of 21 studies containing 6021 patients fitted into Meta analysis-1.The results indicated that PD-L1 high-expression accompanied with a worse overall survival(OS)(HR=1.28,95%Cl:1.01-1.62,P=0.04)in gastric cancer,while no correlation with disease-free survival(DFS)(HR=0.88,95%CI:0.53-1.45,P=0.61).Subgroup analysis showed that high PD-L1 expression was closely connected with age(OR=0.84,95%Cl:0.71-0.99,P=0.04),depth of tumor infiltration(OR=0.58,95%Cl:0.36-0.93,P=0.02),lymph-node metastasis(OR=0.61,95%Cl:0.41-0.93,P=0.02),distant metastasis(OR=1.52,95%Cl:1.12-2.07,P=0.01),Epstein-Barr virus infection status(OR=0.12,95%Cl:0.05-0.32,P<0.0001),and MET expression status(OR=0.56,95%Cl:0.33-0.95,P=0.03).Meta analysis-2 included 3 studies with a total of 1099 patients.Compared with conventional agents,PD-1/PD-L1 inhibitors were associated with significantly prolonged OS in PD-L1 positive patients(HR=0.80,95%Cl:0.66-0.98,P=0.03).But in PD-L1 negative group,there was no significant difference in OS(HR=1.04,95%Cl:0.76-1.42,P=0.81).Conclusion:High expression of PD-L1 may indicate a worse prognosis in patients with gastric cancer,but these patients are more likely to benefit from anti-PD-1/PD-L1 therapy.In addition,the high expression was positively related to age,lymph node metastasis,depth of tumor invasion,EBV infection and MET status,but negatively associated with distant metastasis.