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

Shuhei Ito, Takeo Fukagawa, Miwa Noda, Qingjiang Hu, Sho Nambara, Dai Shimizu, Yohsuke Kuroda, Hidetoshi Eguchi, Takaaki Masuda, Tetsuya Sato, Hitoshi Katai, Mitsuru Sasako, Koshi Mimori

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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.

Original languageEnglish
Pages (from-to)3755-3763
Number of pages9
JournalAnnals of Surgical Oncology
Volume25
Issue number12
DOIs
Publication statusPublished - Nov 1 2018

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Stomach Neoplasms
Gene Expression
Messenger RNA
Monocytes
T-Lymphocytes
Polymerase Chain Reaction
Survival
Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients. / Ito, Shuhei; Fukagawa, Takeo; Noda, Miwa; Hu, Qingjiang; Nambara, Sho; Shimizu, Dai; Kuroda, Yohsuke; Eguchi, Hidetoshi; Masuda, Takaaki; Sato, Tetsuya; Katai, Hitoshi; Sasako, Mitsuru; Mimori, Koshi.

In: Annals of Surgical Oncology, Vol. 25, No. 12, 01.11.2018, p. 3755-3763.

Research output: Contribution to journalArticle

Ito, S, Fukagawa, T, Noda, M, Hu, Q, Nambara, S, Shimizu, D, Kuroda, Y, Eguchi, H, Masuda, T, Sato, T, Katai, H, Sasako, M & Mimori, K 2018, 'Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients', Annals of Surgical Oncology, vol. 25, no. 12, pp. 3755-3763. https://doi.org/10.1245/s10434-018-6739-4
Ito, Shuhei ; Fukagawa, Takeo ; Noda, Miwa ; Hu, Qingjiang ; Nambara, Sho ; Shimizu, Dai ; Kuroda, Yohsuke ; Eguchi, Hidetoshi ; Masuda, Takaaki ; Sato, Tetsuya ; Katai, Hitoshi ; Sasako, Mitsuru ; Mimori, Koshi. / Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients. In: Annals of Surgical Oncology. 2018 ; Vol. 25, No. 12. pp. 3755-3763.
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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.",
author = "Shuhei Ito and Takeo Fukagawa and Miwa Noda and Qingjiang Hu and Sho Nambara and Dai Shimizu and Yohsuke Kuroda and Hidetoshi Eguchi and Takaaki Masuda and Tetsuya Sato and Hitoshi Katai and Mitsuru Sasako and Koshi Mimori",
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T1 - Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients

AU - Ito, Shuhei

AU - Fukagawa, Takeo

AU - Noda, Miwa

AU - Hu, Qingjiang

AU - Nambara, Sho

AU - Shimizu, Dai

AU - Kuroda, Yohsuke

AU - Eguchi, Hidetoshi

AU - Masuda, Takaaki

AU - Sato, Tetsuya

AU - Katai, Hitoshi

AU - Sasako, Mitsuru

AU - Mimori, Koshi

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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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