Serum levels of soluble programmed death-ligand 1 (sPD-L1): A possible biomarker in predicting post-treatment outcomes in patients with early hepatocellular carcinoma.

Background: There have been great advances in hepatocellular carcinoma management over the last years. However, there are still no prognostic biomarkers that can identify patients who will benefit the most from curative treatments. We aimed to investigate whether sPD-L1 levels measured before curative treatment is a prognostic biomarker of survival in patients with HCC.

Methods: HCC patients from a prospectively collected database were selected and soluble programmed death-ligand1(sPD-L1) levels were determined. The association of sPD-L1 levels and overall survival (OS) and disease-free survival (DFS) was assessed.

Results: One hundred twenty-one patients with HCC were included. The best cut-off value of sPD-L1 for both DFS and OS was 96 pg/mL. Patients with a high sPD-L1 value (>96 pg/mL) had a shorter disease free survival and OS (hazard ratio 5.42, 95% confidence interval 2.28-12.91, p < 0.001, and hazard ratio 9.67, 95% confidence interval 4.33-21.59, p < 0.001). High sPD-L1 levels were associated with mortality independently from other known survival predictors. We found a positive correlation between sPD-L1 and PD-L1 expression in cancer cells (p = 0.01). In 16 out of 38 patients, sPD-L1 levels decreased from baseline value on week 6 after treatment and in 22 out of 38 patients, sPD-L1 levels increased from the baseline value. However, fluctuations of sPD-L1 in time had no influence on survival (p = 0.148).

Conclusion: We conclude that a high sPD-L1 level is a biomarkerfor a poor outcome in HCC. The predictive value of sPD-L1 levels for a successful anti-PD1/PD-L1 therapy should be investigated in the future.