Abstract
The expression of Programmed cell Death Ligand 1 (PD-L1) is observed in many malignant tumors and is associated with poor prognosis including Gastric Cancer (GC). The relationship between PD-L1 expression and prognosis, however, is controversial in GC. This paper purports to use a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in GC. For this study, the following databases were searched for articles published from June 2003 until February 2017: PubMed, EBSCO, Web of Science and Cochrane Library. The baseline information extracted were: authors, year of publication, country where the study was performed, study design, sample size, follow-up time, baseline characteristics of the study population, pathologic data, overall survival (OS). A total of 15 eligible studies covering 3291 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The analysis showed that the expression level of PD-L1 was associated with the overall survival in GC (Hazard Ratio, HR = 1.46, 95%CI = 1.08–1.98, P = 0.01, random-effect). In addition to the above, subgroup analysis showed that GC patients with deeper tumor infiltration, positive lymph-node metastasis, positive venous invasion, Epstein-Barr virus infection positive (EBV+), Microsatellite Instability (MSI) are more likely to expression PD-L1. The results of this meta-analysis suggest that GC patients, specifically EBV+ and MSI, may be prime candidates for PD-1 directed therapy. These findings support anti-PD-L1/PD-1 antibodies as a kind of immunotherapy which is promising for GC.
Highlights
Worldwide, gastric cancer (GC) is the fourth most common malignant disease in males and the third leading cause of cancer mortality in males, especially in Eastern Asia, Central and Eastern Europe, and South America, and lowest in Northern America and most parts of Africa[1]
Through a meta-analysis, this review focuses on Programmed cell Death Ligand 1 (PD-L1) expression and its association with clinical outcomes in GC
The analysis suggested that for the following exploratory subgroup: Asian, stages II-III, cut-off value of more than 50% and the cytoplasmic and nuclear PD-L1 expression location within the tumor cell, the P values demonstrated a positive association with the overall survival (OS) in GC (Table 3)
Summary
Gastric cancer (GC) is the fourth most common malignant disease in males (fifth in females) and the third leading cause of cancer mortality in males (fifth in females), especially in Eastern Asia ( in Korea, Mongolia, Japan, and China), Central and Eastern Europe, and South America, and lowest in Northern America and most parts of Africa[1]. The therapeutic efficacy of all immune-checkpoint blockers is not satisfied[2,3,4,5]. No phase III clinical trials on the immune-checkpoint blockers have been conducted on GC patients. Some clinical trials have indicated that monoclonal antibodies that target PD-1 or its receptor PD-L1 prevent the inhibitory effects of PD-1/PD-L1 pathway and enhance T cell functions, leading to impressive outcomes in patients with cancers[6,7,8,9]. From[10], ‘the predictive effects of PD-L1 in response to PD-1/PD-L1 antibodies in GC are not conclusive and the indication of PD-L1 expression in tumors remains controversial and needs to be further investigated’
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