Prognostic Significance of LGR5 Expression in High－Grade Hepatocellular Carcinoma

Background: HCC is a leading cause of cancer-related deaths. The role of LGR5, a cancer stem cell marker, in HCC remains unclear. Methods: This study evaluated LGR5 expression in 50 primary solitary HCC cases using RNAscope, a highly sensitive RNA ISH　method, and assessed its clinicopathological features and prognosis. Results: LGR5 was expressed in some normal hepatocytes, particularly smaller cells, suggesting its involvement in regeneration. In HCC, LGR5 expression was detected in 25 cases. High LGR5 expression in the tumor center was significantly associated with high-grade HCC (p=0.0491). At the invasion front, high LGR5 expression was correlated with high-grade HCC (p=0.0140) and larger tumor size (＞5 cm) (p=0.0334). 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=0.0449). 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=0.0124) and larger tumor size (＞5 cm) (HR, 6.36; 95% CI, 1.57－25.84; p=0.0096). LGR5 expression at the invasion front was not significantly associated with either OS or RFS.Conclusions: These findings suggest that LGR5 expression is associated with aggressive HCC characteristics and poor prognosis, highlighting its potential as a prognostic biomarker in HCC.