Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection

• Published in: Oncotarget 2017-10, Vol.8 (47), p.82399-82414
• Main Authors: Kwon, Mi Jung, Kim, Kab-Choong, Nam, Eun Sook, Cho, Seong Jin, Park, Hye-Rim, Min, Soo Kee, Seo, Jinwon, Choe, Ji-Young, Lee, Hye Kyung, Kang, Ho Suk, Min, Kyueng-Whan
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.19390

Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial. We performed hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers. A multiplex polymerase chain reaction with five quasimonomorphic markers was performed for MSI. PD-L1 expression was observed in 123 cases (31.2%), and clinicopathological features such as MET overexpression, high pT stage, and a lack of lymphatic invasion represent significant risk factors associated with PD-L1 overexpression in gastric cancers. No associations of EBV, MSI, or mucin phenotype with PD-L1 expression were statistically significant. PD-L1 expression was a strong indicator for worse overall survival (OS) but borderline significant in disease-free survival (DFS). A combined analysis of PD-L1 and MET expression indicated that the PD-L1+/MET+ subgroup showed the worst prognosis when compared to the PD-L1-/MET- subgroup, which had the best clinical outcome. Furthermore, PD-L1 overexpression exhibited poor prognosis in terms of both OS and DFS in EBV-negative, microsatellite stable, and intestinal mucin phenotype tumors. In conclusion, this is the first study to evaluate the overexpression of MET as a risk factor for PD-L1 positivity in gastric cancer tissue as well as the reliability and prognostic relevance of PD-L1/MET co-expression after surgery.