Soluble PD-L1 Expression in Circulation as a Predictive Marker for Recurrence and Prognosis in Gastric Cancer: Direct Comparison of the Clinical Burden Between Tissue and Serum PD-L1 Expression
- 116 Downloads
This study assessed programmed cell death ligand 1 (PD-L1) expression in primary tissues and soluble PD-L1 (sPD-L1) concentration in matched preoperative serum in gastric cancer (GC) patients to perform direct comparison between tissue and serum PD-L1 expression and to clarify the prognostic implication in GC.
The study enrolled 180 GC patients who underwent surgery for GC at the authors’ institution. The study evaluated tissue PD-L1 expression using immunohistochemistry and quantified sPD-L1 concentration in preoperative serum using enzyme-linked immunosorbent assay in GC patients.
The findings showed that PD-L1 was overexpressed in GC tissues compared with normal mucosa. Tissue PD-L1 expression was significantly higher in the GC patients with advanced T stage, presence of lympho-vascular invasion, lymph node metastasis, and peritoneal metastasis. Furthermore, elevated tissue PD-L1 expression was significantly associated with poor prognosis for overall survival (OS) and disease-free survival (DFS). Serum sPD-L1 was significantly higher in the GC patients than in the healthy volunteers. Although serum sPD-L1 was not correlated with any clinicopathologic factors, the patients with high serum sPD-L1 showed poorer OS and DFS than those with low sPD-L1. Multivariate analyses showed that both elevated tissue PD-L1 and serum sPD-L1 were independent prognostic factors for poor OS [tissue PD-L1: hazard ratio (HR), 4.28; 95% confidence interval (CI), 1.43–12.8; P = 0.0094 vs. serum sPD-L1: HR, 11.2; 95% CI, 3.44–36.7; P = 0.0001] and poor DFS (tissue PD-L1: HR, 6.96; 95% CI, 2.48–19.6; P = 0.0002 vs. serum sPD-L1: HR, 8.7; 95% CI, 3.16–23.9; P < 0.0001) for the GC patients. Furthermore, infiltrative CD8- and Foxp3-positive T cells were significantly increased in the GC patients with elevated tissue PD-L1 expression.
Both serum sPD-L1 and tissue PD-L1 expression may serve as predictive biomarkers for recurrence and prognosis in GC patients.
The authors thank Yuki Orito and Amphone Okada for their excellent technical assistance. They also thank the Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript. A part of this study was supported by a Grant in Aid for Scientific Research (16K10533) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Study concept and design (TS, YT, YO, TS, KM); provision of samples (TI, SI, HF, HY, JH, SY, MO, TA, MK); acquisition of data (TS, YO, AY, LY, AN, TS); analysis and interpretation of data (TS, YT, YO, HY, SY, MO); statistical analysis (TS, YT, YO); drafting the manuscript (TS, YT, YO, MK).
There are no conflicts of interest.
- 13.Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71.CrossRefGoogle Scholar
- 26.Wang L, Wang H, Chen H, et al. Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma. Oncotarget. 2015;6:41228–36.Google Scholar
- 28.Ha H, Nam AR, Bang JH, et al. Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy. Oncotarget. 2016;7:76604–12.Google Scholar
- 29.Lin G, Fan X, Zhu W, et al. Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer. Oncotarget. 2017;8:83986–94.Google Scholar
- 35.Tamura T, Ohira M, Tanaka H, et al. Programmed death-1 ligand-1 (pdl1) expression is associated with the prognosis of patients with stage II/III gastric cancer. Anticancer Res. 2015;35:5369–76.Google Scholar
- 39.Ju X, Shen R, Huang P, et al. Predictive relevance of PD-L1 expression with pre-existing TILs in gastric cancer. Oncotarget. 2017;8:99372–81.Google Scholar