2019 Fiscal Year Annual Research Report
Prognostic impact of immune-related gene expression in preoperative peripheral blood from gastric cancer patients
| Project/Area Number |
17K10593
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| Research Institution | Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers |
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Principal Investigator |
伊藤 修平 公立学校共済組合九州中央病院(臨床研究センター), 臨床研究センター, 研究員 (10706914)
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| Co-Investigator(Kenkyū-buntansha) |
室 圭 愛知県がんセンター(研究所), がん予防研究分野, 研究員 (10501687)
三森 功士 九州大学, 大学病院, 教授 (50322748)
深川 剛生 国立研究開発法人国立がん研究センター, 中央病院, 医長 (60313152)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | PD-1 / PD-L1 / CD8 / 胃癌 / 予後因子 / バイオマーカー |
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| Outline of Annual Research Achievements |
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). 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.
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