Journal of Cancer Research and Clinical Oncology

, Volume 142, Issue 8, pp 1727–1738 | Cite as

Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer

  • Naoki TakahashiEmail author
  • Satoru Iwasa
  • Yusuke Sasaki
  • Hirokazu Shoji
  • Yoshitaka Honma
  • Atsuo Takashima
  • Natsuko Tsuda Okita
  • Ken Kato
  • Tetsuya Hamaguchi
  • Yasuhide Yamada
Original Article – Cancer Research



Immune checkpoint molecules are key targets for the treatment of various malignancies. Due to the heterogeneity of advanced gastric cancer (GC), the role of programmed cell death ligand 1 (PD-L1) expression as a tumor biomarker remains controversial. In this study, the prognostic value of soluble PD-L1 (sPD-L1) levels in serum samples was assessed in patients with metastatic GC.


All patients received first-line treatment with fluoropyrimidine and platinum chemotherapy, and trastuzumab was added for HER2-positive patients. Serum levels of sPD-L1 were measured by enzyme-linked immunosorbent assay.


Among 75 metastatic GC patients, the median serum sPD-L1 level was 0.704 ng/ml (range <0.156–3.214). Serum sPD-L1 was significantly higher in patients with a high versus a low white blood cell count at baseline. When the cutoff value was set as the median, multivariate analyses showed that high sPD-L1 levels were associated with worse overall survival compared with low sPD-L1 levels (HR 2.218, 95 % CI 1.139–4.320, P = 0.019). Regardless of HER2 status, overall survival tended to be shorter in patients with high sPD-L1 compared with low sPD-L1. There was no significant association between sPD-L1 level and progression-free survival on the first-line treatment of metastatic GC.


High serum levels of sPD-L1 correlated with worse overall survival on the first-line chemotherapy in metastatic GC patients.


Gastric cancer Prognostic factor PD-L1 Serum 



We gratefully appreciate the participation of the patients and their families in this study, and we would like to thank all co-investigators for their contributions: Ms. Hideko Morita and Mrs. Noriko Abe (serum sample preparation).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance with the ethical standards of the national regulations and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent of Biobank of National Cancer Center and using the clinical data was obtained from all individual participants included in the study.

Supplementary material

432_2016_2184_MOESM1_ESM.docx (21 kb)
Supplementary material 1. Summary of first-line treatment (A) and subsequent treatment (B) (DOCX 21 kb)
432_2016_2184_MOESM2_ESM.docx (20 kb)
Supplementary material 2. Prognostic analyses of progression-free survival by uni- and multivariate analyses (DOCX 20 kb)
432_2016_2184_MOESM3_ESM.docx (22 kb)
Supplementary material 3. Difference in patient characteristics by serum sPD-L1 levels using the median as the cutoff value (DOCX 22 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Naoki Takahashi
    • 1
    Email author
  • Satoru Iwasa
    • 1
  • Yusuke Sasaki
    • 1
  • Hirokazu Shoji
    • 1
  • Yoshitaka Honma
    • 1
  • Atsuo Takashima
    • 1
  • Natsuko Tsuda Okita
    • 1
  • Ken Kato
    • 1
  • Tetsuya Hamaguchi
    • 1
  • Yasuhide Yamada
    • 1
  1. 1.Gastrointestinal Medical Oncology DivisionNational Cancer Center HospitalTokyoJapan

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