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

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.

• Authors: Eiji Oki, Shinji Okano, Hiroshi Saeki, Yuichiro Umemoto, Koji Teraishi, Yu Nakaji, Koji Ando, Yoko Zaitsu, Nami Yamashita, Masahiko Sugiyama, Yuichiro Nakashima, Kippei Ohgaki, Yoshinao Oda, Yoshihiko Maehara
• Journal: Oncology (Oncology) Vol. 93 Issue 6 Pg. 387-394 ( 2017) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 28910818 (Publication Type: Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

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

Topics

• 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)