Prognostic and clinicopathological value of PD-L2 in lung cancer: A meta-analysis

•Programmed death ligand-2 (PD-L2) has been widely detected in lung cancer.•PD-L2 overexpression indicates poor prognosis in lung cancer.•PD-L2 overexpression is associated with smoking, PD-L1 expression and vascular invasion. The prognostic role of programmed death ligand-2 (PD-L2) expression in lung cancer has been widely studied, however, the results are controversial. Accordingly, we investigated the prognostic and clinicopathological value of PD-L2 in patients with lung cancer in this meta-analysis. Relevant studies were systematically searched in the PubMed, Web of Science, EMBASE, ClinicalTrials.gov., Scopus, and Cochrane Library until July 10, 2020. The hazard ratio (HR), odds ratio (OR), and their corresponding 95% confidence intervals (CIs) were calculated. Thirteen studies with 3107 participants were included. High PD-L2 expression was associated with poor overall survival (OS) (HR 1.248, 95% CI: 1.071–1.455, p = 0.004) and worse disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS) (HR 1.224, 95% CI: 1.058–1.417, p = 0.007) in lung cancer. Furthermore, unfavorable OS was found in lung adenocarcinoma (HR 1.349, 95% CI: 1.051–1.731, p = 0.019), but not in other pathological types (HR 1.192, 95% CI: 0.982–1.447 p = 0.076) with higher PD-L2 expression in our subgroup analysis. Concerning the clinicopathological characteristics, high PD-L2 expression was associated with smoking (OR 0.725, 95% CI: 0.591–0.890, p = 0.002) and PD-L1 (OR 1.607, 95% CI:1.115–2.314, p = 0.011) and vascular invasion (OR 1.500, 95% CI: 1.022–2.203, p = 0.039). PD-L2 overexpression might predict a poor prognosis in lung cancer patients after surgery. PD-L2 expression might be a potential biomarker for PD-1/PD-L1-targeted immunotherapy in lung cancer, which should be investigated in future studies.