The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer

J Cancer Res Clin Oncol. 2020 Oct;146(10):2547-2557. doi: 10.1007/s00432-020-03314-7. Epub 2020 Jul 15.

Abstract

Introduction: Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC.

Materials and methods: The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells.

Results: The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043).

Conclusion: Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymph-node metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.

Keywords: ANAX2; CD44; CSC; Colorectal cancer; DCLK1; Lgr5.

MeSH terms

  • Aged
  • Annexin A2 / metabolism
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Doublecortin-Like Kinases
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / metabolism*
  • Tissue Array Analysis

Substances

  • ANXA2 protein, human
  • Annexin A2
  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Intracellular Signaling Peptides and Proteins
  • LGR5 protein, human
  • Receptors, G-Protein-Coupled
  • DCLK1 protein, human
  • Doublecortin-Like Kinases
  • Protein Serine-Threonine Kinases