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Published on: January 22, 2018
Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma
Eiji Oki1, Shinji Okano, Hiroshi Saeki
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Objectives:
Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer.
Materials And Methods:
We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45.
Results:
Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells.
Conclusions:
PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1.
Insights
Programmed death-ligand 1 (PD-L1) expression in gastric cancer correlates with poor survival and tumor invasion. Human epidermal growth factor receptor 2 (HER2) signaling influences PD-L1 expression, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Programmed death 1 (PD-1) is an immunoinhibitory receptor targeted in cancer immunotherapy.
- Investigating Programmed death-ligand 1 (PD-L1) expression in gastric cancer is crucial for understanding tumor immune evasion.
Purpose of the Study:
- To report the expression of PD-L1 in surgically resected gastric cancer.
- To investigate the correlation between PD-L1 expression, Human epidermal growth factor receptor 2 (HER2) signaling, and patient survival.
Main Methods:
- Immunohistochemistry was used to detect PD-L1 expression in 144 gastric cancer samples.
- HER2 expression and PTEN loss of heterozygosity were assessed.
- RNA interference (siRNA) was employed to downregulate HER2 in MKN45 gastric cancer cells, with PD-L1 assessed via flow cytometry.
Main Results:
- PD-L1 overexpression was significantly correlated with tumor invasion (p=0.011) and associated with poor survival.
- PD-L1 positivity increased with higher HER2 scores in clinical samples.
- siRNA-mediated HER2 downregulation significantly reduced PD-L1 protein expression in MKN45 cells.
Conclusions:
- PD-L1 expression is linked to poor survival in gastric cancer.
- HER2 signaling pathways influence PD-L1 expression in gastric cancer.
- PTEN and HER2 are potential biomarkers for developing PD-L1 blocking antibodies in gastric cancer therapy.
