PD-L1 expression and patient outcomes in gastrointestinal neuroendocrine neoplasm: a meta-analysis

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is a known prognostic and therapeutic marker in malignant tumors. This meta-analysis aimed to investigate the association of PD-L1 expression with the clinicopathological parameters and survival outcomes of gastrointestinal neuroendocrine neoplasms (NENs). METHODS: PubMed, EMBASE, Web of Science, OVID Medline, the Cochrane Library, and Google Scholar were searched for relevant studies June 30, 2020. Studies reporting PD-L1 immunohistochemistry of gastrointestinal NEN with associated survival data or clinicopathological parameters were included. RESULTS: In total, 10 studies were included. Odd ratios (ORs) were combined to evaluate association between PD-L1 expression and clinicopathological parameters. Hazard ratios (HR) and standard errors were combined to evaluate the association between PD-L1 expression and overall survival. PD-L1 expression was significantly associated with higher tumor grade [OR: 3.42; 95% confidence interval (CI): 2.00–5.85, P<0.05] and lymph node metastasis (OR: 1.94; 95% CI: 1.13–3.34, P=0.02). However, PD-L1 expression was not associated with age, sex, and tumor stage. The pooled hazard ratio (HR: 2.45, 95% CI: 1.20–4.98, P<0.05) showed a significant association between PD-L1 expression and shorter overall survival. DISCUSSION: The results of this meta-analysis show that PD-L1 expression in tumor cells of gastrointestinal NEN can be used as a biomarker of worse survival and important clinicopathological parameters. Further, it can also be used as a therapeutic biomarker for developing novel treatment modalities that can improve prognosis. Although the results of this meta-analysis are more robust than those of the individual studies analyzed, this study also has several limitations. Further studies with a larger study population and consistent method for evaluating PD-L1 expression are needed to validate our results.