Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma

Oncology. 2017;93(6):387-394. doi: 10.1159/000479231. Epub 2017 Sep 15.

Abstract

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.

Keywords: Gastric cancer; Human epidermal growth factor receptor 2; Immunotherapy; Phosphatase and tensin homolog; Programmed death 1 ligand 1.

MeSH terms

  • B7-H1 Antigen / genetics*
  • Carcinoma / genetics*
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / genetics
  • Programmed Cell Death 1 Receptor / genetics
  • Receptor, ErbB-2 / genetics*
  • Stomach Neoplasms / genetics*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • PTEN Phosphohydrolase