Clinical significance and gene expression study of human hepatic stellate cells in HBV related-hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research

Shuang-Jian Qiu²  Jian Sun¹  Jia Fan¹  Jian Zhou¹  Yun-Feng Cheng²  Hong-Wei He¹  Xiao-Yan Cai¹  Jia-Xing Wang¹  Yong Yi¹  Han Wu¹  Rui Liao¹ 

[1] Key Laboratory of Carcinogenesis and Cancer Invasion, the Chinese Ministry of Education, Shanghai, China;Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China

关键词: Hepatocellular carcinoma;    Gene expression;    Phenotype;    Prognosis;    Hepatic stellate cell;   

Others  :  825225
DOI  :  10.1186/1756-9966-32-22

 received in 2013-02-25, accepted in 2013-04-14,  发布年份 2013

【 摘 要 】

Background

Peritumoral activated hepatic stellate cells (HSCs) are versatile myofibroblast-like cells closely related with hepatocellular carcinoma (HCC) progression. So far, comprehensive comparison of gene expression of human HSCs during hepatocarcinogenesis is scanty. Therefore, we identified the phenotypic and genomic characteristics of peritumoral HSCs to explore the valuable information on the prognosis and therapeutic targets of HBV related HCC.

Methods

A tissue microarray containing 224 HBV related HCC patients was used to evaluate the expression of phenotype markers of HSCs including α-SMA, glial fibrillary acidic protein (GFAP), desmin, vinculin and vimentin. HSCs and cancer associated myofibroblasts (CAMFs) were isolated from normal, peritumoral human livers and cancer tissues, respectively. Flow cytometry and gene microarray analysis were performed to evaluate the phenotypic changes and gene expression in HCC, respectively.

Results

Peritumoral α-SMA positive HSCs showed the prognostic value in time to recurrence (TTR) and overall survival (OS) of HCC patients, especially in early recurrence and AFP-normal HCC patients. Expression of GFAP positive HSCs cell lines LX-2 was significantly decreased after stimulation with tumor conditioned medium. Compared with quiescent HSCs, peritumoral HSCs and intratumoral CAMFs expressed considerable up- and down-regulated genes associated with biological process, cellular component, molecular function and signaling pathways involved in fibrogenesis, inflammation and progress of cancer.

Conclusions

Peritumoral activated HSCs displayed prognostic value in HBV related-HCC, and their genomic characteristics could present rational biomarkers for HCC risk and promising therapeutic targets.

【 授权许可】

   
2013 Liao et al.; licensee BioMed Central Ltd.

【 图 表 】

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