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ABSTRACT: BACKGROUND AND AIM: SOX6, a member of the D subfamily of sex determining region y-related transcription factors, plays critical roles in cell fate determination, differentiation and proliferation. It has been identified as a tumor suppressor or an oncogene in different human cancers. However, the role of SOX6 in the development and progression of hepatocellular carcinoma (HCC) has not been explored. The aim of this study was to investigate the expression of SOX6 in HCC and determine its correlation with tumor progression and prognosis. METHODS: 130 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 SOX6 expression in the respective tumors. RESULTS: Q-PCR, immunohistochemistry and Western blotting consistently confirmed the decreased expression of SOX6 at both mRNA and protein levels in HCC tissues compared with their adjacent nonneoplastic tissues (P<0.01). Additionally, the expression of SOX6, determined by immunohistochemistry, was negatively correlated with the tumor stage (P=0.003) and serum AFP (P=0.02). Moreover, HCC patients with lower SOX6 expression had worse 5-year disease-free survival and 5-year overall survival than those with high SOX6 expression (P=0.006 and 0.001, respectively). Furthermore, the Cox proportional hazards model showed that the decreased expression of SOX6 was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR]=2.398, 95% confidence interval [CI]=1.601-5.993, P=0.01) and 5-year overall survival (HR=3.569, CI=1.381-7.290, P=0.008) in HCC. CONCLUSION: These findings provide evidence for the first time that SOX6 expression was decreased in HCC, which correlated with poor prognosis, suggesting that SOX6 may be a novel and potential prognostic marker for HCC.
Cancer epidemiology. 05/2013;
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ABSTRACT: MicroRNA-372 (miR-372) has been demonstrated to play a crucial role in cellular proliferation and apoptosis of cancer cells. However, its effects in hepatocellular carcinoma (HCC) have not been explored. The aim of this study was to investigate the clinical significance of miR-372 in human HCC. Quantitative RT-PCR was performed to detect miR-372 expression in HCC clinical samples and cell lines. Then, Kaplan-Meier and Cox proportional regression analyses were performed to determine the association of miR-372 expression with survival of HCC patients. Moreover, the effects of miR-372 on tumorigenicity of HCC cell lines were evaluated by in vitro assays. miR-372 expression in HCC tissues was significantly higher than in the corresponding normal adjacent liver tissues (P < 0.001). There was a correlation between miR-372 upregulation and advanced TNM stage of HCC patients (P = 0.02). In addition, HCC patients with higher miR-372 expression had significantly poorer recurrence-free survival (P = 0.006) and overall survival (P = 0.001). Multivariate analysis revealed that high miR-372 expression was an independent predictor of poor prognosis (for recurrence-free survival: Hazard Ratio [HR] 6.826, P = 0.01; for overall survival: HR 9.533, P = 0.008). Moreover, in vitro assays demonstrated that the ectopic expression of miR-372 may significantly promote the cellular proliferation, invasion, and migration of HCC cell lines. Our findings showed that miR-372 may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. Furthermore, miR-372 has been identified as a promoter for tumorigenicity of HCC cells, suggesting that it might be a prospective therapeutic target for HCC.
Molecular and Cellular Biochemistry 01/2013; · 2.06 Impact Factor
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ABSTRACT: We previously showed that high expression levels of SOX9 correlate with hepatocellular carcinoma (HCC) progression. However, the exact role that SOX9 plays in HCC remains unclear. In this study, we firstly confirmed that miRNA-101 directly targets SOX9 in HCC. Ectopic expression of miR-101 significantly inhibited HCC cell proliferation and tumorigenicity by targeting SOX9. Moreover, the down-regulation of miR-101 in clinical HCC tissues correlates with tumor aggressiveness and poor prognosis. Therefore, miR-101 may suppress HCC tumor progression by down-regulating SOX9. MiR-101 may be a potential prognostic marker and therapeutic target for HCC.
FEBS letters 11/2012; · 3.54 Impact Factor
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ABSTRACT: OBJECTIVE: L1 cell adhesion molecule (L1CAM), as a member of the immunoglobulin superfamily, has recently been observed in a variety of human malignancies. However, no data of L1CAM are available for hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of L1CAM in HCC and determine its correlation with tumor progression and prognosis. METHODS: 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 L1CAM expression in the respective tumors. RESULTS: Immunohistochemistry, Western blotting, and Q-PCR consistently confirmed the overexpression of L1CAM in HCC tissues compared with their adjacent nonneoplastic tissues at both protein and gene level (both P <0.01). Additionally, the high expression of L1CAM was significantly associated with advanced tumor stage (P = 0.02) and advanced tumor grade (P = 0.03), respectively. Moreover, HCC patients with high L1CAM 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 L1CAM over-expression was an independent poor prognostic factor for both 5-year disease-free survival (P = 0.02) and 5-year overall survival (P = 0.008) in HCC. CONCLUSION: Our data suggest for the first time that L1CAM expression in HCC was significantly correlated with the advanced tumor progression and was an independent poor prognostic factor for both overall survival and disease-free survival in patients with HCC.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1970024872761542.
Diagnostic Pathology 08/2012; 7(1):96. · 1.64 Impact Factor
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ABSTRACT: 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: http://www.diagnosticpathology.diagnomx.eu/vs/9029740396926377.
Diagnostic Pathology 04/2012; 7:44. · 1.64 Impact Factor
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ABSTRACT: Bone morphogenetic protein (BMP) 4 plays a crucial role in tumor invasion and metastasis of various human cancers. However, little is known about the correlation of BMP4 expression with clinical aggressiveness and prognosis in hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of BMP4 in HCC and determine its correlation with tumor progression and prognosis. Immunohistochemistry assay was used to determine the expression of BMP4 in HCC and corresponding paracarcinomatous tissues from 156 patients. The potential prognostic value of BMP4 was investigated by comparing the survival rates between the BMP4-positive and BMP4-negative HCC patients. Immunohistochemically, BMP4 protein expression in the HCC tissues (120/156, 76.9%) was significantly higher than that in the paracarcinomatous tissues (19/156, 12.2%, P < 0.01). The expression of BMP4 in HCC was associated with number of tumor nodules (P = 0.02), Edmondson grade (P = 0.03), TNM stage (P = 0.009), and vascular invasion (P = 0.006). In univariate survival analysis, the significant associations of the BMP4 protein overexpression with shortened patients' overall and disease-free survival were found (P = 0.001 and 0.006, respectively). Furthermore, its expression was found to be an independent factor for predicting both overall (P = 0.009) and disease-free survival (P = 0.022) of HCC in multivariate analysis. Our data suggest for the first time that BMP4 is overexpressed in HCC tissues and may also act as a novel marker for predicting the recurrence and prognosis of HCC patients after surgery.
Pathology & Oncology Research 02/2012; 18(3):635-40. · 1.37 Impact Factor
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Jingmin Zhao,
Suxian Zhao,
Guangde Zhou,
Li Liang, Xiaodong Guo,
Panyong Mao,
Xianzhi Zhou,
Haibin Wang,
Yuemin Nan,
Dongping Xu,
Jun Yu
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ABSTRACT: Lipopolysaccharide (LPS) is suspected to trigger primary biliary cirrhosis (PBC) in susceptible individuals, yet the precise mechanism of its effect in PBC remains largely unknown. The aim of this study was to investigate altered responses to LPS ligand for Toll-like receptors (TLRs) in pathogenesis of PBC in vivo and in vitro.
In vivo, we investigated levels of LPS and pro-inflammatory cytokines in sera and expression of LPS receptors in liver tissues from 162 patients with PBC, 325 patients with other liver diseases and 80 healthy controls. In vitro, altered responses to LPS on monocytes and cultured human biliary epithelial cells (BECs) from patients with PBC were determined.
Significantly higher levels of LPS in patients with PBC were detected, compared with patients with other liver diseases and healthy controls. Immunohistochemically, expression of TLR4, CD14, CD68 and NF-κB was significantly enhanced in liver tissues from patients with PBC. Before LPS stimulation, we found significantly higher serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8 in patients with PBC than those in healthy controls. After LPS stimulation, TLR4 expression and pro-inflammatory cytokine production in CD14-positive monocytes and cultured BEC from patients with PBC increased significantly.
These results indicated that patients with PBC were prone to exhibit higher serum LPS level, hypersensitivity of monocytes and BEC to LPS, and enhanced production of pro-inflammatory cytokines. LPS altered expression of TLR4, CD14 and NF-κB on monocytes and BEC, which may be implicated in the pathogenesis and progression of PBC.
Scandinavian journal of gastroenterology 01/2011; 46(4):485-94. · 2.08 Impact Factor
