Prognostic value of programmed death-ligand 1 (PD-L1) expression in ovarian clear cell carcinoma

Abstract

ObjectiveProgrammed death-ligand 1 (PD-L1) was expressed in various tumors and antibodies targeting its receptor programmed cell death-1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and its correlation with clinicopathologic features and clinical outcomes in ovarian clear cell carcinoma (OCCC).MethodsThe PD-L1 expression was measured by tissue-microarray-based immunohistochemistry from 122 eligible patients diagnosed with OCCC. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model.ResultsOverall, high PD-L1 expression (PD-L1high) was observed in 44.7% (55/123) of OCCC patients, and was strongly associated with advanced stages (p=0.020), positive ascitic fluid (p=0.016), platinum-resistant (PR) disease (p=0.045), and recurrence (p=0.038). Moreover, patients with PD-L1high were associated with poorer OS (hazard ratio [HR]=2.877; p=0.001) and PFS (HR=1.843; p=0.021) than those with low PD-L1 expression (PD-L1low). In subgroup analysis, PD-L1high patients experienced a poorer PFS (HR=1.926; p=0.044) and OS (HR=2.492; p=0.021) than PD-L1low cases among advanced stages (III–IV), but this difference was not observed in stage I–II patients. Meanwhile, PD-L1high was associated with poorer prognosis than PD-L1low in PR patients (OS, HR=2.253; p=0.037; PFS, HR=1.448; p=0.233). Multivariate analysis revealed that PD-L1high and advanced stages (III–IV) were adverse independent prognosticators for both PFS (HRPD-L1=2.0; pPD-L1=0.038; HRstage=10.2; pstage<0.001) and OS (HRPD-L1=3.0; pPD-L1=0.011; HRstage=14.3; pstage<0.001).ConclusionPD-L1high might serve as a risk factor for PFS and OS in patients with OCCC. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCCC.

<p>LncRNA EMX2OS Induces Proliferation, Invasion and Sphere Formation of Ovarian Cancer Cells via Regulating the miR-654-3p/AKT3/PD-L1 Axis</p>

“…28 High expression of PD-L1 was correlated with worse overall survival in multiple cancer types, including OC. 29 Tumor cell-intrinsic PD-L1 was shown to promote tumor-initiating cell generation in OC. 30 Our data provided the first demonstration that PD-L1 serves as a crucial downstream effector of AKT3, and targeting PD-L1 might possibly retard the initiation and progression of OC induced by the EMX2OS/miR-654/AKT3 pathway, although this possibility requires further investigation.…”

Programmed Death Ligand 1 (PD-L1) Expression in Epithelial Ovarian Cancer: A Comparison of Type I and Type II Tumors

“…Published data regarding the prognostic value of PD-L1 expression in type I EOC specifically is extremely limited. A study by Zhu et al, (2017) conducted in 122 women with ovarian clear cell carcinoma was the first report to evaluate the prognostic significance of PD-L1 expression. The study noted that high expression of PD-L1 was associated with advanced stages, recurrence, and poorer survival.…”

Patient inflammatory status and CD4+/CD8+ intraepithelial tumor lymphocyte infiltration are predictors of outcomes in high-grade serous ovarian cancer

“…Previous reports suggest that PDL1 overexpression and TILs can serve as prognostic for poorer and better survival, respectively, in epithelial ovarian cancers [25,26], therefore next we determined the presence of TILs by IHC against CD3+, CD4+ and CD8+, additionally we assessed PDL1. Fig.…”