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

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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)387-394
Number of pages8
JournalOncology (Switzerland)
Volume93
Issue number6
DOIs
Publication statusPublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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