Measurement of soluble PD-1 and soluble PD-L1 as well as PD-L1 and PD-1 from perioperative patients with gastric carcinoma.

Abstract

Till now, no experiment has been performed to detect programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1), soluble PD-L1/soluble PD-1 simultaneously in perioperative patients of gastric carcinoma. Our experiment aims at determining the clinical significance and possible mechanism of soluble PD-L1/soluble PD-1 in gastric carcinoma. Thirty patients undergone gastrectomy were selected as the experimental group. Tissue's programmed death ligand 1 and peripheral programmed death 1 were detected using immunofluorescence and flow cytometry. Soluble PD-L1 and soluble PD-1 were detected using enzyme-linked immunosorbent assay. First, preoperative programmed death 1 was higher than control group and decreased to normal post-operatively. Preoperatively ,elevated levels of programmed death 1 on cluster of differentiation (CD)4 T cells indicated less lymphatic metastasis (P<0.01) and small tumor volume (P<0.01); elevated programmed death 1 of CD8 T cells indicated big tumor volume (P<0.01) and well histological differentiation (P<0.01). Second, preoperative soluble PD-L1 and soluble PD-1 are lower than in control group. Post-operatively, the soluble PD-1 rose to normal, but the soluble PD-L1 showed no change. Third, programmed death ligand 1 can be observed in carcinoma tissue. Fourth, the area under the curve of soluble PD-1 (0.675) for diagnosis was worse than that of soluble PD-L1 (0.885). Kaplan-Meier analysis showed that soluble PD-1<245.26pg/ml in post-operative serum predicted a poor prognosis (overall survival percentage: 60%) at 2 years (P<0.05). Multivariate analysis revealed that carcinoembryonic antigen (>5ng/l) and soluble PD-1 after gastrectomy (>245.26pg/ml) were independent prognostic factors for overall survival (hazard ratio: 20.812, 95% confidence interval: 1.217-355.916, P=0.036; hazard ratio: 0.028, 95% confidence interval: 0.001-0.786, P=0.036, respectively). We propose that soluble PD-1 combined with programmed death ligand 1 are effective not only in protecting T cells from the adhesion by programmed death ligand 1 but also in preventing the occurrence and the development of tumor as well. Through multivariate analysis, we found that soluble PD-1 was an independent protective factor for post-operative prognosis of gastric carcinoma patients, which indirectly verified the vital function of soluble PD-1. Soluble PD-1 might be promising predictive biomarkers for the diagnosis and prognosis of gastric carcinoma patients.