High expression of truncated GLI3 is associated with poor overall survival in patients with non-small cell lung cancer

Abstract

The hedgehog (Hh) pathway is involved in embryogenesis and organogenesis. GLI3 is one of the zinc-finger transcription factors in the Hh signaling pathway, which exist in both full-length (GLI3FL) and truncated (GLI3TR) forms. We investigated GLI3 expression in patients with non-small cell lung cancer (NSCLC). The role of GLI3 in lung carcinogenesis and its correlation with clinicopathological factors and overall survival (OS) in patients with NSCLC were explored. GLI3FL and GLI3TR expression were analyzed immunohistochemically in 330 and 352 evaluable NSCLC tissues respectively. The association between GLI3FL and GLI3TR expression and clinicopathological parameters and OS were statistically analyzed. GLI3FL immunohistochemical staining could be observed in the cytoplasm, while GLI3TR staining could be observed in nucleus of malignant epithelial cells. High level expression of GLI3FL and GLI3TR were 52.7% and 45.2% respectively. GLI3FL was not significantly correlated with any clinicopathological parameter and survival. However, high-expression of GLI3TR was significantly associated with lymph node metastasis (P = 0.013) and poor OS (28.4 vs. 40.8 months, P = 0.010). In patients with adenocarcinoma of high and low GLI3TR expression, the median OS were 25.7 and 50.6 months respectively (P = 0.004). Multivariate analysis showed that GLI3TR expression (P = 0.036), tumor differentiation (P < 0.001), disease stage (P < 0.001) were independent prognostic factors for patients with NSCLC. Overexpression of GLI3TR in NSCLC, especially in adenocarcinoma, is associated with poor prognosis. GLI3TR expression is an independent prognostic factor in OS. GLI3TR may play an important role in the tumorigenesis of NSCLC.