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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

Tsunehiko Shigemori MD, Yuji Toiyama MD, PhD, FACS, Yoshinaga Okugawa MD, PhD, Akira Yamamoto MD, Chengzeng Yin MD, Aya Narumi MD, Takashi Ichikawa MD, Shozo Ide MD, PhD, Tadanobu Shimura MD, PhD, Hiroyuki Fujikawa MD, PhD, Hiromi Yasuda MD, PhD, Junichiro Hiro MD, PhD, Shigeyuki Yoshiyama MD, PhD, Masaki Ohi MD, PhD, Toshimitsu Araki MD, PhD, Masato Kusunoki MD, PhD
Translational Research and Biomarkers
Volume 26, Issue 3 / March , 2019

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

Both serum sPD-L1 and tissue PD-L1 expression may serve as predictive biomarkers for recurrence and prognosis in GC patients.

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