The clinical and prognostic significance of LGR5 in GC: A meta-analysis of IHC assay and bioinformatics analysis

Recently, leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a newly identified cancer stem cell marker and Wnt target gene. However, the role of LGR5 in gastric cancer (GC) remains uncertain. This study was performed to investigate the effect of LGR5 expression in GC. The eligible studies were searched via electronic databases. The odds ratios (ORs) with 95% confidence intervals (CIs) or hazard ratios (HRs) with 95% CIs were applied to estimate the effect of LGR5. Further bioinformatics validation data were used to confirm our results. Eleven studies consisting of 2,646 GC patients were identified. LGR5 expression was not associated with age, gender, tumor stage, T stage, tumor size, lymphatic invasion, lymph node metastasis, and distal metastasis. LGR5 expression was related to tumor type (intestinal vs. diffuse: OR=2.25, p=0.032). LGR5 expression was negatively correlated with tumor grade (grade 3-4 vs. grade 1-2: OR = 0.40, p=0.033). Further TCGA validation data also showed similar findings, and LGR5 expression was also found to have a negative association with tumor grade. LGR5 expression was associated with worse overall survival (OS) using multivariate Cox analysis (HR=2.54, p=0.009). Further bioinformatics data showed that LGR5 expression was still correlated with shorter OS in 876 GCs. LGR5 expression was negatively correlated with tumor grade and its expression was higher in intestinal-type than in diffuse-type. Moreover, LGR5 may be a potential prognostic factor for survival prediction in GC.