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

Abstract

BackgroundSOX9 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.MethodsOne-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.ResultsImmunohistochemistry, 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.ConclusionOur 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 slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9029740396926377.

MicroRNA‐101 suppresses SOX9‐dependent tumorigenicity and promotes favorable prognosis of human hepatocellular carcinoma

“…For example, Wang et al [12] detected the expression of SOX9 in prostate cancer cells contributes to tumor growth and invasion; Aleman et al [13] found that SOX9 hypermethylation in primary bladder tumours was present more than half of the cases and was significantly associated with tumour grade and overall survival; Malki et al [14] shown that the embryonic male prostaglandin D synthase/ SOX9 pathway was expressed at both the RNA and protein levels in different types of human ovarian tumors, pointing to SOX9 as a possible diagnostic marker for ovarian carcinomas. Especially, the previous study of our group detected the up-regulation of SOX9 at mRNA and protein levels in clinical HCC tissues compared with their adjacent non-neoplastic tissues [15]. Our data also indicated that high SOX9 expression is associated with advanced tumor progression and poor clinical outcome of HCC patients [15].…”

“…Especially, the previous study of our group detected the up-regulation of SOX9 at mRNA and protein levels in clinical HCC tissues compared with their adjacent non-neoplastic tissues [15]. Our data also indicated that high SOX9 expression is associated with advanced tumor progression and poor clinical outcome of HCC patients [15]. On the basis of these findings, the aim of the present study was to elucidate the mechanism of SOX9 plays in HCC.…”

Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis

“…Recent reports have established a direct link between EMT and a gain of stem/progenitor cell properties (22), which is supported by our mouse models because tumor cells undergoing EMT clearly expressed stem cell markers. The expression of stem cell markers such as CD44 and Sox9 has been reported to be associated with poor prognosis in patients with HCC (28,29). Interestingly, E-cadherin , and vimentin using a human HCC tissue array that contains 60 HCC samples (E-cadherin-negative, n = 28; -positive, n = 32).…”

Sox9 and programming of liver and pancreatic progenitors

“…In this process, Notch appears to play a fundamental role; inactivation or activation of Notch signaling in acinar cells and hepatocytes does not cause any lesions, but the combination of Notch activation and carcinogenic signals (oncogenic Kras induction in acinar cells and thioacetamide administration or AKT overexpression in hepatocytes) results in conversion to a duct cell type (76)(77)(78). Interestingly, Sox9 is overexpressed in human hepatocellular carcinoma, and its expression is associated with tumor progression and poor prognosis (79). More recently, ectopic expression of Sox9 and Hnf6, another pancreatic duct marker, has been reported in human metaplastic acinar cells associated with pancreatitis and pancreatic adenocarcinoma (80).…”