Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer

Abstract

Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis. This study assessed the clinical significance of PD-L1 mRNA expression in blood specimens obtained from patients with gastric cancer. Peripheral blood specimens were collected before treatment from 124 patients with gastric cancer. The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death-ligand 1 mRNA expression was significantly higher in patients with advanced gastric cancer than in patients with early gastric cancer (P = .002). Moreover, PD-L1 expression correlated significantly with depth of tumor invasion, distant metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients with high PD-L1 expression showed significantly poorer prognosis than those with low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1 expression as an independent prognostic factor. Expression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer.

Keywords: gastric cancer; liquid biopsy; peripheral blood; prognosis; programmed death-ligand 1.

Figure 1

Immunocytochemical staining for programmed death‐ligand 1 (PD‐L1) expression in gastric cancer cell lines using DAPI (A,D,G) and anti‐PD‐L1 mAb–phycoerythrin staining (B,E,H). C,F,I, Merged staining of PD‐L1‐PE and DAPI. PD‐L1 is expressed in tumor cells of MKN‐7, MKN‐74, and NCI‐N87 cell lines. Scale bar = 100 μm (original magnification, ×400)

Figure 2

Reverse transcription–PCR assay for programmed death‐ligand 1 (PD‐L1) mRNA expression in gastric cancer cell lines and clinical blood specimens obtained from patients with early and advanced gastric cancer. Horizontal bars indicate mean PD‐L1 mRNA copy number

Figure 3

Receiver operating characteristic curve for discriminating gastric cancer patients with and without distant metastasis based on programmed death‐ligand 1 mRNA expression. Area under the curve was 0.772

Figure 4

Kaplan–Meier survival curves for patients with gastric cancer based on status of programmed death‐ligand 1 (PD‐L1) mRNA expression. Patients with high PD‐L1 expression had significantly poorer prognosis than those with low PD‐L1 expression (P < .0001)