<i>LGR5</i> 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 <i>LGR5</i> 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 <i>LGR5</i> was expressed in some normal hepatocytes, particularly smaller cells, suggesting its involvement in regeneration. In HCC, <i>LGR5</i> expression was detected in 25 patients. High <i>LGR5</i> expression in the tumor center was significantly associated with high-grade HCC (<i>P</i> = .0491). At the invasion front, high <i>LGR5</i> expression was correlated with high-grade HCC (<i>P</i> = .0140) and larger tumor size (>5 cm) (<i>P</i> = .0334). A Kaplan-Meier analysis showed no significant difference in overall survival (OS) between the groups. However, high <i>LGR5</i> expression at the tumor center was linked to shorter recurrence-free survival (RFS) (<i>P</i> = .0449). On multivariate analysis, high <i>LGR5</i> expression at the tumor center was significantly associated with shorter RFS (HR, 6.77; 95% CI, 1.51-30.31; <i>P</i> = .0124) and larger tumor size (>5 cm) (HR, 6.36; 95% CI, 1.57-25.84; <i>P</i> = .0096). The <i>LGR5</i> expression at the invasion front was not significantly associated with either OS or RFS. The present findings suggest that <i>LGR5</i> 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.