AUTHOR=Yang Huayu , Zhou Xiaoxiang , Sun Lejia , Mao Yilei 

TITLE=Correlation Between PD-L2 Expression and Clinical Outcome in Solid Cancer Patients: A Meta-Analysis

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00047

DOI=10.3389/fonc.2019.00047

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway are a paradigm-shifting cancer therapy. Programmed cell death ligand 2 (PD-L2) is another ligand of PD-1, but its prognostic significance in solid cancer patients after surgery remains controversial. In this study, we aimed to reveal the prognostic implication of PD-L2 in solid tumors through a meta-analysis.</p><p><bold>Methods:</bold> We searched PubMed, Embase and the Cochrane library for studies reporting the relationship between PD-L2 expression and prognosis or clinicopathological features in solid cancer patients after surgery from inception to January 2018, with language restricted to English. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were determined to explore the prognostic value of PD-L2 expression. Odds ratios (ORs) were also calculated to investigate the relationship between PD-L2 expression and clinicopathological parameters.</p><p><bold>Results:</bold> Sixteen studies incorporating 3,533 patients were included in our meta-analysis. The pooled results revealed that PD-L2 overexpression was a weak negative predictor for overall survival (OS; HR = 1.38, 95% CI = 1.05–1.81, <italic>P</italic> = 0.021), as well as a strong predictor for poor disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.44, 95% CI = 1.15–1.81, <italic>P</italic> = 0.001). In subgroup analyses, high PD-L2 expression revealed an unfavorable prognostic prediction for OS in hepatocellular carcinoma (HCC) (HR = 1.60, 95% CI = 1.12–2.29, <italic>P</italic> = 0.011) and for DFS/PFS in HCC (HR = 1.50, 95%CI = 1.04–2.16, <italic>P</italic> = 0.031) as well as clear cell renal cell carcinoma (HR = 1.45, 95% CI = 1.03–2.03, <italic>P</italic> = 0.033). Moreover, PD-L2 expression implied a weak trend toward the presence of lymphatic metastasis (presence vs. absence, OR = 1.61, 95% CI = 0.98–2.65, <italic>P</italic> = 0.061).</p><p><bold>Conclusion:</bold> High PD-L2 expression may promote tumor metastasis and predict unfavorable prognosis in solid cancer patients after surgery, especially in HCC.</p>