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

Title
Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection
Author
민경환
Keywords
gastric cancer; programmed death ligand-1 protein; MET protein; prognosis; microsatellite instability
Issue Date
2017-07
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET, v. 8, no. 47, page. 82399-82414
Abstract
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 in situ 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.
URI
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=19390&path[]=62024https://repository.hanyang.ac.kr/handle/20.500.11754/115009
ISSN
1949-2553
DOI
10.18632/oncotarget.19390
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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