Leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) belongs to the leucine-rich repeat-containing subgroup of the G-protein-coupled 7-transmembrane protein superfamily [1]. LGR6 has homology to LGR4 and LGR5 [1], and is a stem cell marker for hair follicles [2], lung [3], and mammary gland [4]. LGR6 is involved in tissue development, regeneration, and injury repair.

LGR4, LGR5, and LGR6 have important effects in the activation of the Wnt/β-catenin signaling pathway by binding R-spondin ligands [5], [6] and are associated with tumor progression and invasion [7]. LGR6 is also involved in cancer initiation and progression in lung [8], breast [4], and ovarian cancer [9].

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis [10], and improvements are required in treatment outcomes. To improve the survival rate of patients, the establishment of new biomarkers and targets is required. There are several reports of LGR6 expression in ESCC [11]. Although a previous report showed that LGR6 is a target gene of the Wnt/β-catenin signaling pathway [12], little is known about the relationship between LGR6 and β-catenin expression in ESCC. There is no report of mRNA expression analysis by RNA in situ hybridization for LGR6, but in the same LGR family, RNA in situ hybridization of LGR5 is reported to be more reliable than immunohistochemistry [13]. Therefore, we identified LGR6 expression using RNAscope, a highly sensitive RNA in situ hybridization method. The aim of this study was to elucidate the clinicopathological significance of LGR6 expression and the relationship between LGR6 and β-catenin in ESCC, and to examine the possibility of their application to ESCC treatment.