Journal
FRONTIERS IN ONCOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2019.00047
Keywords
PD-L2; prognostic biomarker; solid tumor; immune checkpoint; meta-analysis
Categories
Funding
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001]
- National High-tech Research and Development Projects (863) [2015AA020303]
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Background: 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. Methods: 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 (Cls) 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. Results: 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, P = 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, P = 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, P = 0.011) and for DFS/PFS in HCC (HR = 1.50, 95%Cl = 1.04-2.16, P = 0.031) as well as clear cell renal cell carcinoma (HR = 1.45, 95% CI = 1.03-2.03, P = 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, P = 0.061). Conclusion: High PD-L2 expression may promote tumor metastasis and predict unfavorable prognosis in solid cancer patients after surgery, especially in HCC.
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