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

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.