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

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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

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Acknowledgments

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).

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Authors and Affiliations

  1. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Naoki Takahashi, Satoru Iwasa, Yusuke Sasaki, Hirokazu Shoji, Yoshitaka Honma, Atsuo Takashima, Natsuko Tsuda Okita, Ken Kato, Tetsuya Hamaguchi & Yasuhide Yamada

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  1. Naoki Takahashi
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  2. Satoru Iwasa
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Correspondence to Naoki Takahashi.

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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.

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

Electronic supplementary material

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Supplementary material 1. Summary of first-line treatment (A) and subsequent treatment (B) (DOCX 21 kb)

432_2016_2184_MOESM2_ESM.docx

Supplementary material 2. Prognostic analyses of progression-free survival by uni- and multivariate analyses (DOCX 20 kb)

432_2016_2184_MOESM3_ESM.docx

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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Takahashi, N., Iwasa, S., Sasaki, Y. et al. Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer. J Cancer Res Clin Oncol 142, 1727–1738 (2016). https://doi.org/10.1007/s00432-016-2184-6

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