Background: Although glioma-associated oncogene homolog 1 (Gli1) is a key mediator of the Hedgehog pathway, Gli1 involvement in the maintenance of cancer stem-like cells (CSCs) in prostate cancer (PCa) is unclear.
Methods: Herein, we assessed the expression of Gli1 and its relationship with cancer stemness genes, cell cycle markers, epithelial-mesenchymal transition (EMT), and signaling pathway genes in 145 paraffin-embedded PCa tissue samples using immunohistochemistry. In addition, we further confirmed the correlation between Gli1 and CSC marker in PC3 cells using immunofluorescence imaging.
Results: High Gli1 expression was significantly associated with advanced primary tumor stage, positive lymph node metastasis, advanced clinical stage, and HIF-1α expression. The microvessel density was significantly higher in the Gli1 positive-cases than in the negative-cases. Furthermore, Gli1 expression was positively correlated with stemness markers CD44. Survival analysis demonstrated that Gli1 and CD44 were strongly associated with the worse clinical outcome and an independent poor prognostic factor for overall survival. The enrichment analysis revealed that Gli1 was not correlated with E-cadherin, while positively correlated with Snail and vimentin. Notably, Gli1 expression was positively associated with the expression of cell cycle regulating genes such as cyclin D1, p21 and CDK4. Additionally, Gli1 expression was positively correlated with pPI3K p85, pAkt-Ser473 and NF-κB p65 expression.
Conclusions: Our results indicate that Gli1 is a potential diagnostic marker of CSCs and that Gli1 expression is strongly associated with epithelial-mesenchymal transition in PCa via PI3K/Akt/NF-κB signaling.
Keywords: Glioma-associated oncogene homolog 1; PI3K/Akt/NF-κB signaling; cancer stem-like cells; prognosis; prostate cancer.
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