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

Article (PDF Available)inDiagnostic Pathology 7(1):44 · April 2012with36 Reads
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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    • "Through upregulation of Oct4, it is involved in maintenance of cancer stem-like properties including self-renewal, chemoresistance, and tumorigenicity [162]. Guo et al. [163] first analyzed SOX9 protein and mRNA expression in human HCC tissue and found that it was associated with patient clinical outcome. The overexpression of SOX9 was observed in tumor tissues with higher tumor stage, poorer disease-free survival, and poorer overall survival of HCC patients. "
    [Show abstract] [Hide abstract] ABSTRACT: Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with “stem-like” characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a “global” marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies.
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    • "GS and HSP70 have been shown to be useful for the diagnosis of malignant hepatocellular neoplasms (Di Tommaso et al., 2007). CK19 (Uenishi et al., 2003), Sox9 (Guo et al., 2012), and GS (Osada et al., 2000 ) are also reported in HCC diagnosis with bad prognosis. Finally, AFP is positively identified in one-third of HCCs, mainly in higher histological grades (Zhao et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via T helper 17 (Th17) lymphocytes and interleukin 17A (IL-17A). This induces white adipose tissue neutrophil infiltration mediating insulin resistance (IR) and fatty acid release, stored in liver as triglycerides, causing NASH. NASH and subsequently HCC are prevented by pharmacological suppression of Th17 cell differentiation, IL-17A blocking antibodies, and genetic ablation of the IL-17A receptor in myeloid cells. Human hepatitis, fatty liver, and viral hepatitis-associated HCC exhibit increased IL-17A correlating positively with steatosis. IL-17A blockers may prevent IR, NASH, and HCC in high-risk patients.
    Article · Jul 2016 · Diagnostic Pathology
    • "Recently important progress has been made with using comprehensive approaches to identify the molecular diversity in HCC. A large number of genetic and epigenetic abnormalities were found during the process of HCC de- velopment5678. Consequently, many new prognostic biomarkers of HCC have been described [9,10]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background MicroRNA-106b (miR-106b) is a member of the miR-106b¿~¿25 cluster. It has been reported that miR-106b acts as an oncogene and is upregulated in many human cancers. However, the prognostic value of miR-106b in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the clinical significance of miR-106b expression in HCC.Methods We determined the expression level of miR-106b in 104 cases of paired HCC and adjacent non-tumor tissues by quantitative real-time PCR (qRT-PCR). The correlation between miR-106b expression and prognosis of HCC was studied by univariate and multivariate analysis. Multivariate analysis of the prognostic factors was performed with Cox proportional hazards model.ResultsMiR-106b expression was significantly upregulated in as high as 76.0% of HCC tissues, compared with their non-tumor counterparts (P <¿0.001). High miR-106b expression was significantly associated with large tumor size (P =¿0.019) and vascular invasion (P =¿0.016). Kaplan-Meier analysis showed that patients with high miR-106b expression had a worse overall survival than patients with low miR-106b expression (log-rank P =¿0.004). The multivariate Cox regression analysis indicated that miR-106b expression was an independent prognostic factor for overall survival (HR, 2.002; 95% CI, 1.130-6.977; P =¿0.027).Conclusion Our data indicated that miR-106b expression was significantly upregulated in HCC and could serve as a potential unfavorable prognostic biomarker.Virtual SlidesThe virtual slide(s) for this article can be found here:
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