LGR5 Expression Is Associated With Prognosis in High-Grade Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. The role of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a cancer stem cell marker, in HCC remains unclear. This study evaluated LGR5 expression in 50 primary solitary HCC patients using RNAscope, a highly sensitive RNA in situ hybridization method, and assessed its clinicopathological and prognostic significance. The LGR5 was expressed in some normal hepatocytes, particularly smaller cells, suggesting its involvement in regeneration. In HCC, LGR5 expression was detected in 25 patients. High LGR5 expression in the tumor center was significantly associated with high-grade HCC (P = .0491). At the invasion front, high LGR5 expression was correlated with high-grade HCC (P = .0140) and larger tumor size (>5 cm) (P = .0334). A Kaplan-Meier analysis showed no significant difference in overall survival (OS) between the groups. However, high LGR5 expression at the tumor center was linked to shorter recurrence-free survival (RFS) (P = .0449). On multivariate analysis, high LGR5 expression at the tumor center was significantly associated with shorter RFS (HR, 6.77; 95% CI, 1.51-30.31; P = .0124) and larger tumor size (>5 cm) (HR, 6.36; 95% CI, 1.57-25.84; P = .0096). The LGR5 expression at the invasion front was not significantly associated with either OS or RFS. The present findings suggest that LGR5 expression is associated with aggressive HCC characteristics and increased risk of recurrence, highlighting its potential as a prognostic marker for RFS in high-grade HCC.