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Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma

Authors :
Bin Xu
Qi Zheng
Zi Chen
Xin-Yu Huang
Thomas J. Re
Zi-Li Huang
Xiu-Yan Huang
Zhao-You Tang
Source :
Journal of Experimental & Clinical Cancer Research : CR
Publication Year :
2016
Publisher :
BioMed Central, 2016.

Abstract

Background Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. Methods An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed. Results Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo. Conclusions The poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0361-8) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
17569966 and 03929078
Volume :
35
Database :
OpenAIRE
Journal :
Journal of Experimental & Clinical Cancer Research : CR
Accession number :
edsair.doi.dedup.....c205380a4ec78369fc52c96a0c33264e