Expressions of Carbohydrate Response Element Binding Protein and Glucose Transporters in Liver Cancer and Clinical Significance
Expressions of Carbohydrate Response Element Binding Protein and Glucose Transporters in Liver Cancer and Clinical Significance
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碳水化合物反应元件结合蛋白和葡萄糖转运蛋白在肝癌中的表达及临床意义
DOI：
10.1007/s12253-019-00708-y
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发表时间：
2020-04-01
影响因子：
2.8
通讯作者：
Gu, Jiang
中科院分区：
文献类型：
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作者：
Lei, Yu;Hu, Qiaoling;Gu, Jiang
碳水化合物反应元件结合蛋白（ChREBP）是一种葡萄糖敏感转录因子，介导糖酵解和脂肪生成基因的诱导。我们研究了ChREBP和葡萄糖转运蛋白（GLUT）在人肝细胞癌（HCC）中的表达模式及其与HCC进展的关系。对正常肝组织、癌旁组织和不同分期肝癌组织进行ChREBP、GLUT 2和GLUT 1免疫组织化学染色。用单因素方差分析分析HCC恶性程度对蛋白表达的影响。采用Pearson相关性检验分析蛋白表达之间的相关性。我们发现ChREBP蛋白表达与肝脏恶性程度呈正相关。与正常肝组织相比，GLUT 2蛋白在人HCC中的表达显著降低，并且其在HCC中的表达与恶性程度呈负相关（p < 0.001）。相反，GLUT 1在癌细胞中显著增加，并且其表达与恶性程度呈正相关（p < 0.001）。此外，GLUT 1表达与ChREBP表达呈正相关（r = 0.481，p < 0.0001，n = 70），但与GLUT 2表达呈负相关（r =-0.320，p = 0.007，n = 70）。值得注意的是，表达ChREBP的肝细胞不表达GLUT 2，但表达GLUT 1。这是首次报道ChREBP和GLUT 2/GLUT 1在肝癌中的表达及其相互关系。表达模式与肝癌的恶性程度有关，这一信息将有助于评估肝癌的临床行为和治疗。
Carbohydrate response element binding protein (ChREBP) is a glucose-sensing transcription factor that mediates the induction of glycolytic and lipogenic genes in response to glucose. We investigated the expression patterns of ChREBP and glucose transporters (GLUTs) in human hepatocellular carcinoma (HCC) and their association with HCC progression. ChREBP, GLUT2 and GLUT1 immunohistochemistry were performed on liver tissue array containing normal liver tissue, HCC adjacent tissue and cancer tissue of different HCC stages. The effect of HCC malignancy on protein expression was analyzed with one-way ANOVA. The correlations between protein expressions were analyzed with Pearson Correlation test. We found that ChREBP protein expression tended to be positively correlated to liver malignancy. GLUT2 protein expression was significantly reduced in human HCC as compared to normal liver tissue and its expression in HCC was inversely associated to malignancy (p < 0.001). In contrast, GLUT1 was significantly increased in cancer cells and its expression was positively correlated to malignancy (p < 0.001). Furthermore, GLUT1 expression was positively associated to ChREBP expression (r = 0.481, p < 0.0001, n = 70) but negatively correlated to GLUT2 expression (r = -0.320, p = 0.007, n = 70). Notably, ChREBP-expressing hepatocytes did not express GLUT2 but GLUT1. This is the first report unveiling expressions of ChREBP and GLUT2/GLUT1 and their relations in HCC. The expression patterns are related to malignancy and this information would facilitate evaluation of clinical behavior and treatment of HCC.