Lei Yu, Hu Qiaoling, Gu Jiang
Department of Pathology and Pathophysiology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, 515041, Guangdong, China.
Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713, GZ, Groningen, The Netherlands.
Pathol Oncol Res. 2020 Apr;26(2):1331-1340. doi: 10.1007/s12253-019-00708-y. Epub 2019 Aug 12.
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.
碳水化合物反应元件结合蛋白（ChREBP）是一种葡萄糖感应转录因子，可介导糖酵解和脂肪生成基因对葡萄糖的应答诱导。我们研究了ChREBP和葡萄糖转运蛋白（GLUTs）在人类肝细胞癌（HCC）中的表达模式及其与HCC进展的关联。对包含正常肝组织、HCC癌旁组织以及不同HCC阶段癌组织的肝脏组织芯片进行ChREBP、GLUT2和GLUT1免疫组化。采用单因素方差分析分析HCC恶性程度对蛋白表达的影响。用Pearson相关检验分析蛋白表达之间的相关性。我们发现ChREBP蛋白表达倾向于与肝脏恶性程度呈正相关。与正常肝组织相比，GLUT2蛋白表达在人类HCC中显著降低，且其在HCC中的表达与恶性程度呈负相关（p < 0.001）。相反，GLUT1在癌细胞中显著增加，其表达与恶性程度呈正相关（p < 0.001）。此外，GLUT1表达与ChREBP表达呈正相关（r = 0.481，p < 0.0001，n = 70），但与GLUT2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GLUT2但表达GLUT1。这是首次揭示ChREBP和GLUT2/GLUT1在HCC中的表达及其关系的报告。这些表达模式与恶性程度相关，该信息将有助于评估HCC的临床行为和治疗。
