The expression status and prognostic significance of programmed cell death 1 ligand 1 in gastrointestinal tract cancer: a systematic review and meta-analysis

BACKGROUND Programmed cell death 1 ligand 1 (PD-L1) expression has been observed in various malignancies. However, the association between PD-L1 expression and the survival of patients with gastrointestinal tract cancer remains controversial. Besides, the rate of PD-L1 positivity on tumor cells of digestive tract cancer is not clear. Thus, we performed a meta-analysis by incorporating all available evidence to evaluate the rate of PD-L1 positivity and the overall survival (OS) according to PD-L1 status in patients with gastrointestinal tract cancer. METHODS Electronic databases were searched for eligible literature. Hazard ratios (HRs) for OS with 95% confidence intervals (CIs) according to the expression status of PD-L1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on a random-effects model. RESULTS Fifteen studies (only nine reported OS) that involved 2,993 gastrointestinal tract cancer patients stratified by PD-L1 status were eligible for inclusion in our study. We found the PD-L1-positive expression rate was 0.495 (95% CI 0.415-0.576) if 10% was taken as the cut-off value. When the H-score method was used to evaluate PD-L1 expression, it showed that the PD-L1 positive rate was 0.639 (95% CI 0.490-0.765) if the cut-off value was <50, which was higher than when using >50 as the cut-off point (0.449, 95% CI 0.417-0.483). Additionally, PD-L1-positive gastrointestinal tract cancer patients were associated with significantly poorer OS when compared to negative ones (HR 1.61, 95% CI 1.10-2.35, P=0.014). Subgroup analysis presented similar significant results in patients with esophageal cancer (HR 2.56, 95% CI 1.55-4.21, P<0.001). CONCLUSION The positive expression rate of PD-L1 was nearly 50% no matter which method for immunohistochemistry evaluation we chose. Additionally, positive PD-L1 expression status in tumor cells is a risk factor for prognosis of gastrointestinal tract cancer, especially esophageal cancer.