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

Annals of Surgical Oncology volume 25, pages 3755–3763 (2018)Cite this article

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.).

Author information

Author notes

  1. Shuhei Ito MD, PhD

    Present address: Department of Surgery, National Fukuoka-Higashi Medical Center, Koga, Fukuoka, Japan

Authors and Affiliations

  1. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan

    Shuhei Ito MD, PhD, Miwa Noda MD, Qingjiang Hu MD, PhD, Sho Nambara MD, PhD, Dai Shimizu MD, PhD, Yosuke Kuroda MD, PhD, Hidetoshi Eguchi MD, PhD, Takaaki Masuda MD, PhD & Koshi Mimori MD, PhD

  2. Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan

    Takeo Fukagawa MD, PhD, Hitoshi Katai MD, PhD & Mitsuru Sasako MD, PhD

  3. Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan

    Takeo Fukagawa MD, PhD

  4. Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Tetsuya Sato PhD

  5. Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan

    Mitsuru Sasako MD, PhD

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  1. Shuhei Ito MD, PhD
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Corresponding author

Correspondence to Koshi Mimori MD, PhD.

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The authors declare no conflict of interest.

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Supplementary material 1 (XLSX 32 kb)

Supplementary material 2 (XLSX 39 kb)

10434_2018_6739_MOESM3_ESM.pdf

mRNA expression of PD-1, PD-L1, and CD8 in peripheral blood of GC patients with or without preoperative chemotherapy. The median and fold increases of mRNA expression in patients with preoperative chemotherapy versus those without preoperative chemotherapy are shown. The P values were calculated by the Mann–Whitney U test (PDF 128 kb)

10434_2018_6739_MOESM4_ESM.pdf

Survival rates in patients with GC classified by low and high ratio of PD-L1/PD-1 mRNA levels in peripheral blood. The OS of 372 GC patients who underwent surgery and the DFS of 338 GC patients who underwent curative surgery are shown (PDF 45 kb)

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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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  • DOI: https://doi.org/10.1245/s10434-018-6739-4

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