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. 2020;98(7):501-511.
doi: 10.1159/000506075. Epub 2020 May 7.

Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer

Shuhei Ito  1 , Takaaki Masuda  1 , Miwa Noda  1 , Qingjiang Hu  1 , Dai Shimizu  1 , Yosuke Kuroda  1 , Hidetoshi Eguchi  1 , Taro Tobo  2 , Tohru Utsunomiya  3 , Koshi Mimori  4
Affiliations

Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer

Shuhei Ito et al. Oncology. 2020.

Abstract

Introduction: Anti-programmed cell death 1 (PD-1) therapies have shown promising clinical activity against gastric cancer (GC). We evaluated the clinical significance of immune-related gene expression in GC tissues to better understand the tumor immune microenvironment.

Methods: PD-1, PD-1 ligand 1 (PD-L1) and CD8 mRNA levels and clinicopathological factors, including survival, were examined by quantitative RT-PCR in 155 GC patients who underwent surgery. PD-1 and PD-L1 expression in tumor tissue from 24 GC patients was investigated by immunohistochemical analysis.

Results: PD-1, PD-L1 and CD8 mRNA levels were significantly lower in tumor tissue than in normal tissue (p < 0.0001, p < 0.05, and p < 0.0001). GC patients with low PD-1, PD-L1 and CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, PD-L1 and CD8 mRNA levels, respectively (p < 0.001, p < 0.01 and p < 0.05). Low PD-1, PD-L1 and CD8 mRNA levels were more significantly associated with poor prognosis in undifferentiated-type GC patients than in differentiated-type GC patients (PD-1: differentiated p = 0.0071 vs. undifferentiated p = 0.0024; PD-L1: p = 0.6527 vs. p < 0.0001; CD8: p = 0.4465 vs. p < 0.05). Multivariate analysis showed that lymph node metastasis, peritoneal dissemination, distant metastasis, low PD-1 mRNA levels and low CD8 mRNA levels were independent prognostic factors for worse OS (low PD-1 mRNA level: OR 2.16, 95% CI 1.10-4.58, p < 0.05; low CD8 mRNA level: OR 2.55, 95% CI 1.12-6.90, p < 0.05). PD-1 and PD-L1 mRNA levels in immune cells were significantly associated with PD-1 and PD-L1 protein levels (both p < 0.05), respectively.

Conclusions: PD-1, PD-L1 and CD8 mRNA levels may reflect antitumor immunity in GC, and low PD-1 and CD8 mRNA levels are potential predictive biomarkers for poor prognosis in GC patients who underwent surgery.

Keywords: Antitumor immune response; CD8; Gastric cancer; Immune-related gene; PD-1; PD-L1; Prognosis; Surgery.

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