PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer
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Yanhua Wu1, Donghui Cao1, Limei Qu2, Xueyuan Cao3, Zhifang Jia1, Tiancheng Zhao4, Quan Wang3 and Jing Jiang1
1Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin 130021, China
2Department of Pathology, First Hospital of Jilin University, Changchun, Jilin 130021, China
3Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, China
4Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130021, China
Jing Jiang, email: [email protected]
Quan Wang, email: [email protected]
Keywords: gastric cancer, prognosis, PD-L1, tumor infiltrating immune cells, EBV
Received: April 18, 2017 Accepted: June 16, 2017 Published: July 18, 2017
While the prognosis of gastric cancer (GC) remains poor, PD-1 and PD-L1/L2 are promising prognostic biomarkers. We evaluated PD-1 and PD-L1/L2 expression in tumor cells (TCs) and tumor-infiltrating immune cells (TIICs). We determined the Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) infection status in a GC cohort (n=340), then analyzed the relationship between the expression of PD-1, PD-L1/L2 and GC prognosis. We found that PD-1, PD-L1, and PD-L2 mRNA levels were up-regulated in GC tissues, and were positively correlated with one another (P=0.043, P=0.008 and P=0.035). PD-1 protein expression in TIICs was observed in 22.6% of GC patients. The PD-L1 and PD-L2 positivity rates were 40.3% and 53.8% in TCs, respectively, and 60.0% and 60.9% in TIICs, respectively. PD-L1 was up-regulated in EBV-infected GC patients in both TCs (P=0.009) and TIICs (P=0.003). Hp status was not associated with PD-1 or PD-L1/PD-L2 expression. In TIICs, PD-L1 expression was independently associated with better GC prognosis (HR=0.72, 95%CI: 0.53-0.99). Co-expression of PD-1 and PD-L1, but not PD-L2, was a favorable prognostic marker that indicated a dose effect on the mortality risk of GC patients (P-value for trend=0.005). Comprehensive evaluation of PD-1 and PD-L1 in TCs and TIICs could help predict the prognosis of gastric cancers, as well as reveal patients who might benefit from targeted treatment.
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