Expression of glioma-associated oncogene 2 (Gli 2) is correlated with poor prognosis in patients with hepatocellular carcinoma undergoing hepatectomy

Abstract

BackgroundOur previous studies showed that glioma-associated oncogene (Gli)2 plays an important role in the proliferation and apoptosis resistance of hepatocellular carcinoma (HCC) cells. The aim of this study was to explore the clinical significance of Gli2 expression in HCC.MethodsExpression of Gli2 protein was detected in samples from 68 paired HCC samples, the corresponding paraneoplastic liver tissues, and 20 normal liver tissues using immunohistochemistry. Correlation of the immunohistochemistry results with clinicopathologic parameters, prognosis, and the expression of E-cadherin, N-cadherin, and vimentin were analyzed.ResultsImmunohistochemical staining showed high levels of Gli2 protein expression in HCC, compared with paraneoplastic and normal liver tissues (P < 0.05). This high expression level of Gli2 was significantly associated with tumor differentiation, encapsulation, vascular invasion, early recurrence, and intra-hepatic metastasis (P < 0.05). There was a significantly negative correlation between Gli2 and E-cadherin expression (r = −0.302, P < 0.05) and a significantly positive correlation between expression of Gli2 and expression of vimentin (r = −0.468, P < 0.05) and N-cadherin (r = −0.505, P < 0.05). Kaplan-Meier analysis showed that patients with overexpressed Gli2 had significantly shorter overall survival and disease-free survival times (P < 0.05). Multivariate analysis suggested that the level of Gli2 expression was an independent prognostic factor for HCC.ConclusionsExpression of Gli2 is high in HCC tissue, and is associated with poor prognosis in patients with HCC after hepatectomy.

Expression of Hedgehog Pathway Mediator GLI Represents a Negative Prognostic Marker in Human Acute Myeloid Leukemia and Its Inhibition Exerts Antileukemic Effects

“…As in our study, the dysregulated HH signaling is often mirrored by increased expression of downstream transcription factors GLI (18,19). In line with our data, a negative prognostic impact of GLI2 expression was very recently shown for gastric, hepatocellular and oral squamous cell cancer (20)(21)(22).…”

From Normal Development to Disease: The Biochemistry and Regulation of GLI2

“…In transitional cell carcinoma cell lines, overexpression of GLI2 increases the invasive nature of these cells in Matrigel invasion assays [62] . GLI2 expression had been known to be increased in hepatocellular carcinoma when compared to nearby normal liver, but it was also determined that this increase in expression correlated with intrahepatic metastasis and vascular invasion [74] . Lending further explanation to this finding, immunohistochemistry of these tumors revealed that an increase in GLI2 expression also correlated with a decrease in the expression of E-cadherin and an increase in vimentin [74] .…”

Salinomycin exerts anticancer effects on human breast carcinoma MCF-7 cancer stem cells via modulation of Hedgehog signaling

“…It is part of the final step in the pathway that is regulated by the zinc finger transcription factors, Gli1 and Gli2, which are activators of the Hh target genes. It has also been demonstrated that a high expression of Gli1 by immunohistochemistry is an independent risk factor for skip metastasis of axillary lymph nodes in breast cancer [49][50]. The study by Zhang demonstrate that activation of the Hh pathway signified by increased expression of Gli1 does seem to have a correlation with both the development of disease and its aggressiveness, which makes this pathway a potential target for future therapy [50].…”

“…It has also been demonstrated that a high expression of Gli1 by immunohistochemistry is an independent risk factor for skip metastasis of axillary lymph nodes in breast cancer [49][50]. The study by Zhang demonstrate that activation of the Hh pathway signified by increased expression of Gli1 does seem to have a correlation with both the development of disease and its aggressiveness, which makes this pathway a potential target for future therapy [50]. In our study, we found that SMO and Gli1 expressions were significantly reduced by Sal treatment in a dose-dependent manner using western blotting and RT-PCR.…”