Exploring LGR5 as a prognostic marker of extrahepatic cholangiocarcinoma: insights from expression analysis and clinical correlations

Diagn Pathol. 2024 Aug 28;19(1):116. doi: 10.1186/s13000-024-01537-7.

Abstract

Background: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC).

Methods: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed.

Results: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397).

Conclusions: These findings suggest that LGR5 is a promising, novel prognostic marker.

Keywords: Extrahepatic cholangiocarcinoma; Leucine-rich repeat-containing G protein-coupled receptor 5; RNA in situ hybridization.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / metabolism
  • Bile Duct Neoplasms* / mortality
  • Bile Duct Neoplasms* / pathology
  • Biomarkers, Tumor* / analysis
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / metabolism
  • Cholangiocarcinoma* / mortality
  • Cholangiocarcinoma* / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, G-Protein-Coupled* / analysis
  • Receptors, G-Protein-Coupled* / genetics
  • Receptors, G-Protein-Coupled* / metabolism

Substances

  • Receptors, G-Protein-Coupled
  • LGR5 protein, human
  • Biomarkers, Tumor