Gli1 is a potential cancer stem cell marker and predicts poor prognosis in ductal breast carcinoma

Hum Pathol. 2017 Nov:69:38-45. doi: 10.1016/j.humpath.2017.08.038. Epub 2017 Sep 28.

Abstract

Glioma-associated oncogene homolog 1 (Gli1) maintains the cancer stem cell-like characteristics in various tumors. However, its expression in cancer stem cells (CSC) in ductal breast carcinoma has not been well studied. We aimed to characterize Gli1 as a potential CSC marker and investigate its clinical significance in ductal breast carcinoma. Immunohistochemical staining was used to study the relationship of Gli1 to clinicopathologic features, cell cycle regulation-related genes, and CSC markers. Gli1 was expressed to a greater extent in ductal breast carcinoma than in normal breast tissues (P=.002). Its expression was significantly correlated with tumor grade (P=.044), pT stage (P=.017), and molecular subtype (P=.008). Expression was associated, not only with the expression of HIF-1α (P<.001), but also with greater microvessel density (MVD; P=.012). Kaplan-Meier survival analysis revealed that Gli1 was significantly associated with lower overall survival (OS; P=.02). Univariate Cox regression analysis confirmed that Gli1 was a poor prognostic factor for OS (P=.037) and was associated with the expression of the cell cycle-related genes cyclin D1 (P=.011), p21 (P=.009), and pAkt-Thr308 (P=.038). Moreover, Gli1 expression correlated significantly with the expression of two CSC markers, Sox2 (P=.01) and LSD1 (P=.01). Gli1 could be a stem cell marker and an indicator of poor prognosis in patients with ductal breast carcinoma.

Keywords: Cancer stem cell; Ductal breast carcinoma; Gli1; Marker; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / chemistry*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy
  • Cell Cycle Proteins / analysis
  • Chi-Square Distribution
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplastic Stem Cells / chemistry*
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic
  • Phosphorylation
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-akt / analysis
  • Risk Factors
  • Zinc Finger Protein GLI1 / analysis*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • GLI1 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Zinc Finger Protein GLI1
  • Proto-Oncogene Proteins c-akt