Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients

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.

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Acknowledgment

The authors thank all the patients that provided samples for the study. We thank Ms. Kazumi Oda, Ms. Michiko Kasagi, and Ms. Sachiko Sakuma for their technical assistance; Dr. Reiko Takahashi and Dr. Daisuke Oryoji for their advice for flow cytometric analysis; and members of the Department of Surgery, Kyushu University Beppu Hospital for technical assistance and discussion. This work was supported in part by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (C) (Grand 17K10593 to S.I.), Daiwa Securities Health Foundation (to S.I.), and Oita Cancer Research Foundation (to S.I.).

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Correspondence to Koshi Mimori MD, PhD.

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Ito, S., Fukagawa, T., Noda, M. et al. Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients. Ann Surg Oncol 25, 3755–3763 (2018). https://doi.org/10.1245/s10434-018-6739-4

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Keywords

  • Immune-related Genes
  • Preoperative PB
  • Immune-related Gene Expression
  • Gastric Cancer
  • Independent Poor Prognostic Marker