BCL6B expression in hepatocellular carcinoma and its efficacy in the inhibition of liver damage and fibrogenesis.

Weilin Wang,Qifan Yang,Rong Kong,Lufei Zhang,Linshi Zhang,Xiaohu Zhou,Pengfei Huang,Jiang Xu,Lin Zhou,Shusen Zheng,Qingsong Xie,Haiyang Xie,Panyisha Wu,Linghui Chen

doi:10.18632/oncotarget.3857

Weilin Wang, Qifan Yang + Show 12 more

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https://doi.org/10.18632/oncotarget.3857

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Journal: Oncotarget	Publication Date: Apr 27, 2015
Citations: 13	License type: cc-by

Affiliation: First Affiliated Hospital Zhejiang University

Abstract

B cell CLL/lymphoma 6 member B (BCL6B) is expressed in many normal tissues but expressed at very low levels in cancer tissues. It was reported that BCL6B inhibits hepatocellular carcinoma (HCC) metastases, but the exact role of BCL6B in HCC remains to be investigated. BCL6B expression was significantly decreased in HCC tissues compared with paired non-cancer tissues. Low BCL6B expression in tumors was correlated with shorter overall survival in patients, and multivariate Cox regression analysis revealed that BCL6B expression was an independent prognostic factor for human HCC patients. Moreover, a positive correlation between BCL6B expression and hepatic cirrhosis was found in an analysis of HCC clinicopathological characteristics. BCL6B expression was increased in rat fibrotic liver samples in response to liver injury. BCL6B transgenic rats were less susceptible to hepatocellular damage, inflammation and fibrosis. In vitro studies demonstrated that BCL6B inhibited the activation of hepatic stellate cells though upregulation of hepatocyte growth factor. In addition, transcriptomic microarray analysis was performed to explore the mechanisms in which BCL6B confers protection from tumorigenesis. In conclusion, BCL6B plays a pivotal role as a prognostic biomarker for HCC, and the restoration of BCL6B may be a novel strategy as an anti-fibrogenic therapy for human HCC.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and exhibits the third highest mortality rate
A positive correlation between B cell CLL/lymphoma 6 member B (BCL6B) expression and hepatic cirrhosis was found in an analysis of hepatocellular carcinoma (HCC) clinicopathological characteristics
Immunohistochemical staining of the HCC tissues showed predominant localization of the BCL6B protein in the cytoplasm in the adjacent non-tumor tissues but significant downregulation in HCC tissues (Figure 1C). These results were confirmed in tissue microarray (TMA) from 90 HCC patients, which showed a significant decrease in BCL6B expression in 69 of 90 HCC tissue samples (76.7%) compared with matched normal liver tissues (p

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and exhibits the third highest mortality rate. More than 90% of HCCs worldwide develop from a cirrhotic background as a result of chronic hepatitis B or C infection, alcohol abuse, or metabolic syndrome. Most of these cases will die from this complication, since the 5-year survival rate remains a dismal 12% with the currently available therapies [1, 2]. The most well-known profibrogenic mediators expressed by activated HSCs include transforming growth factor beta (TGF-β) and platelet-derived growth factor, whereas hepatocyte growth factor (HGF) functions as an antifibrogenic mediator [9, 10] the effects of HGF in www.impactjournals.com/oncotarget reducing the accumulation of ECM and the development of hepatic fibrosis have been investigated extensively, the exact mechanism regulating HGF expression in HSCs in response to liver injury and inflammation remains unknown

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