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.

Review 서 론최근To combat the associated pandemics of obesity and type 2 diabetes mellitus, clinicians need every tool they can get. Currently, bariatric/metabolic surgery is widely accepted as the most effective treatment for weight loss and glycemic control. Nonetheless, the impact noted in clinical studies seems to have predominantly been on the numerical reductions of bodyweight and blood glucose level after surgery. Past and recent evidence about the role of bariatric surgery in the different stages of the clinical course of type 2 diabetes were presented in this paper. Given the evidence on the efficacy of bariatric surgery for obese patients with type 2 diabetes ranging from pre-diabetes through a long-standing diabetic state with established or end-stage macro-and micro-vascular complications, the overall conclusions are that end organ damage is expected to either stabilize or improve postoperatively in most cases. However, some of these clinical outcomes have not been assessed with a robust method, and many cases are not supported by randomized clinical trials. Available evidence strongly advocates in favor of bariatric surgery in the early phase of this course, possibly in the pre-diabetic or very early diabetic stages. To reserve surgery to more advanced and complicated stages of the disease seems to confer fewer benefits in the clinical course of diabetes and might expose these more frail patients to the possible side effects of a rapid weight loss.