Expression features of SOX9 associate with tumor progression and poor prognosis of hepatocellular carcinoma

Postgraduate Medical School of PLA, Beijing, China.
Diagnostic Pathology (Impact Factor: 2.6). 04/2012; 7(1):44. DOI: 10.1186/1746-1596-7-44
Source: PubMed


SOX9 as a member of the SOX (SRY [sex determining region Y] box) gene superfamily has been previously demonstrated to be a proto-oncogene in a variety of malignancies. However, the clinical significance of SOX9 expression in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of SOX9 in HCC and determine its correlation with tumor progression and prognosis.
One-hundred and thirty HCC patients who had undergone curative liver resection were selected and immunohistochemistry, Western blotting, and quantitative real time polymerase chain reaction (Q-PCR) were performed to analyze SOX9 expression in the respective tumors.
Immunohistochemistry, Western blotting, and Q-PCR consistently confirmed SOX9 overexpression in HCC tissues compared with their adjacent nonneoplastic tissues (P ≪ 0.01). Additionally, immunostaining showed more SOX9 positive cells in the higher tumor stage (T3 ~ 4) and tumor grade (G3) than in the lower tumor stage (T1 ~ 2, P = 0.03) and tumor grade (G1 ~ 2, P = 0.01), respectively. Moreover, HCC patients with high SOX9 expression were significantly associated with lower 5-year overall survival (P ≪ 0.01) and lower 5-year disease-free survival (P ≪ 0.01), respectively. The Cox proportional hazards model further showed that SOX9 over-expression was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 2.621, 95% confidence interval[CI] = 1.548-5.829, P = 0.01) and 5-year overall survival (HR = 3.825, CI = 1.638-7.612, P = 0.003) in HCC.
Our data suggest for the first time that the overexpression of SOX9 protein in HCC tissues is of predictive value on tumor progression and poor prognosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:

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    • "CSCs also express ALDH1, Oct4, Myd88 and EpCAM [47], [51], [57], [60], [78], [79]. An increase in number of CSCs in ovarian tumors correlates with a poor prognosis, including shorter overall and disease free survival [80]–[82]. Development of chemo-resistance of ovarian cancer could be explained by enrichment for CSCs [77], [83]–[85]. In a recent study, Abubaker et al. [53] demonstrated using two ovarian cancer cell lines (epithelial OVCA433 and mesenchymal HEY) enrichment for a population of cells with high expression of CSC markers at the protein as well as mRNA levels after treatment with CIS, paclitaxel and the combination of both. "
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    PLoS ONE 09/2014; 9(9):e107596. DOI:10.1371/journal.pone.0107596 · 3.23 Impact Factor
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    • "Additionally a recent prospective study has shown that the decrease of miR-101 in HCC tissues correlates with tumor aggressiveness and poor prognosis (Zhang et al., 2012a). miRNA-101 targets directly SOX9, whose upregulation has been related to HCC progression (Guo et al., 2012), therefore low levels of this miRNA may be considered a potential prognostic marker of tumor progression. Another miRNA associated significantly with poor prognosis is miR-139, whose downregulation is associated with features of metastatic tumors including microsatellite formation, absence of tumor encapsulation, venous invasion and reduced differentiation (Wong et al., 2011) Recent data indicate that epigenetic inactivation of several miRNAs may also have a significant role in HCC progression. "
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    ABSTRACT: miRNAs are small non-coding RNAs which target complementary mRNAs sequences, usually resulting in gene silencing. They can exhibit oncogenic or tumor suppressor properties, modulating cell homeostasis. Several data have documented that miRNAs are typically deregulated in different types of cancers, including hepatocellular carcinoma (HCC). Some of the miRNAs, such as miR-122, miR-221, miR-1 and miR-21 have been found to repress post-transcriptionally the expression of genes involved in cell cycle regulation, cell proliferation, apoptosis, cell migration and invasion. In HCC serum levels of miR-122, miR-221 and miR-16 have been described deregulated, suggesting that they may be used as molecular targets for early detection, prognosis and treatment. The ov-serpin SerpinB3 was found previously increased in liver tumor cancers and associated with apoptosis resistance, increased cell proliferation and invasiveness. Recent data indicate that this serpin may enhance its oncogenic potential through inhibition of several tumor suppressive miRNAs, typically described in HCC.
    Life sciences 02/2014; 100(1). DOI:10.1016/j.lfs.2014.01.073 · 2.70 Impact Factor
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    • "Liver and HCC Stem Cells Transcriptomic analysis indicates that DEN-induced HcPCs are related to both normal hepatobiliary bipotential stem cells/oval cells and HCC cells. Although HcPCs are not fully transformed, they express several markers—CD44, EpCAM, AFP, SOX9, OV6, and CK19—found to be expressed by HCC stem cells and oval cells (Guo et al., 2012; Mikhail and He, 2011; Terris et al., 2010; Yamashita et al., 2008; Zhu et al., 2010). However, unlike oval cells, which do not express albumin or AFP and do not give rise to liver tumors upon transplantation into MUPuPA mice, HcPCs give rise to HCC after intrasplenic transplantation . "
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    Cell 10/2013; 155(2):384-396. DOI:10.1016/j.cell.2013.09.031 · 32.24 Impact Factor
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