Shuhei Ito1,2, Takeo Fukagawa3,4, Miwa Noda1, Qingjiang Hu1, Sho Nambara1, Dai Shimizu1, Yosuke Kuroda1, Hidetoshi Eguchi1, Takaaki Masuda1, Tetsuya Sato5, Hitoshi Katai3, Mitsuru Sasako3,6, Koshi Mimori7. 1. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan. 2. Department of Surgery, National Fukuoka-Higashi Medical Center, Koga, Fukuoka, Japan. 3. Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan. 4. Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan. 5. Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. 6. Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan. 7. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan. kmimori@beppu.kyushu-u.ac.jp.
Abstract
BACKGROUND: Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. METHODS: The correlation between the preoperative PD-1, PD-L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. RESULTS: The PD-1, PD-L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P < 0.0001). GC patients with low PD-1, high PD-L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, low PD-L1, and high CD8 mRNA levels, respectively (P < 0.01, P < 0.05, and P < 0.05, respectively). Multivariate analysis showed that low PD-1 and high PD-L1 mRNA levels were independent poor prognostic factors for OS (PD-1: HR 2.38, 95% CI 1.27-4.78, P < 0.01; PD-L1: HR 1.81, 95% CI 1.15-2.78, P < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. CONCLUSIONS: The PD-1, PD-L1, and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD-1 and high PD-L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.
BACKGROUND: Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. METHODS: The correlation between the preoperative PD-1, PD-L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. RESULTS: The PD-1, PD-L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P < 0.0001). GC patients with low PD-1, high PD-L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, low PD-L1, and high CD8 mRNA levels, respectively (P < 0.01, P < 0.05, and P < 0.05, respectively). Multivariate analysis showed that low PD-1 and high PD-L1 mRNA levels were independent poor prognostic factors for OS (PD-1: HR 2.38, 95% CI 1.27-4.78, P < 0.01; PD-L1: HR 1.81, 95% CI 1.15-2.78, P < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. CONCLUSIONS: The PD-1, PD-L1, and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD-1 and high PD-L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.