Prognostic significance of soluble forms of the PD-1 receptor and its ligand PD-L1 in gastric cancer

Abstract

Introduction. Despite advances in the diagnosis and drug therapy of some cancers over the past decade, solid tumors, particularly gastric cancer, still have a poor prognosis and remain a leading cause of death worldwide. Therefore, the development of methods for timely diagnosis, identification of new targets for therapy and biochemical prognosis factors is an urgent problem in clinical oncology. In recent years, the focus of clinical attention has been on immune checkpoint receptors and ligands that can identify patients for immunotherapy. The clinical and prognostic significance of the levels of soluble forms of the programmed cell death receptor PD-1 and its ligand PD-L1 in the blood of patients with gastric cancer is currently not fully determined.Aim. Comparative study of the levels of sPD-1 and sPD-L1 in the blood plasma of healthy donors and patients with gastric cancer, taking into account the prevalence of the tumor process and the prognosis of overall survival.Materials and methods. The study included 100 patients with stomach cancer aged from 25 to 81 years (57 men, 43 women), who underwent examination and treatment at the N. N. Blokhin National Medical Research Center for Oncology. The concentration of sPD-L1 and sPD-1 was determined in blood plasma obtained according to standard methods before the start of specific treatment, using reagent kits for enzyme-linked immunosorbent assay “Human PD-L1 Platinum ELISA” and “Human PD-1 ELISA kit” (Affimetrix, eBioscience, USA) in accordance with the manufacturer’s instructions. The content of markers was expressed in picograms (pg) per 1 ml of blood plasma. To compare indicators and analyze their relationships, the nonparametric Mann–Whitney test was used. Overall survival analysis was performed using the Kaplan–Meier method. For all statistical tests, p values <0.05 were considered statistically significant.Results. The analysis did not reveal a connection at a threshold level of sPD-1 of 8.0 pg / ml in the blood plasma of patients with gastric cancer with overall survival rates (p = 0.59). However, an additional analysis conducted in a group of patients with gastric cancer with stages I–II demonstrated that a marker level ≥8.0 pg / ml is a favorable prognostic factor (p = 0.0039), while in advanced stages III–IV the disease it has no prognostic significance. There was no significant correlation between sPD-L1 concentrations in the blood plasma of patients with gastric cancer and overall survival rates (p = 0.35), however, the best long-term results were found at a threshold level of marker concentrations in blood plasma <35 pg / ml.Conclusion. An sPD-1 level ≥8.0 pg / ml can serve as a favorable prognostic factor in stages I–II of gastric cancer, while in advanced stages III–IV of the disease it has no prognostic significance. The prognostic role of sPD-L1 in patients with gastric cancer has not been identified. The study needs to be continued in combination with additional predictive biomarkers for gastric cancer.