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J Exp Clin Cancer Res. 2016 May 26;35(1):85. doi: 10.1186/s13046-016-0361-8.

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

Author information

1
Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, Peoples Republic of China. xyhuang1119@163.com.
2
Department of Radiology, Xuhui Central Hospital, Shanghai, 200031, Peoples Republic of China.
3
Department of General Surgery, The Tenth People's Hospital of Tongji University, Shanghai, 200072, Peoples Republic of China.
4
Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.
5
Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02446, USA.
6
Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, Peoples Republic of China.
7
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, Peoples Republic of China.
8
Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, Peoples Republic of China. xinyuhuang9@163.com.

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.

KEYWORDS:

Hepatocellular carcinoma; Invasion; Metastasis; Metastasis suppressor 1

PMID:
27230279
PMCID:
PMC4881066
DOI:
10.1186/s13046-016-0361-8
[Indexed for MEDLINE]
Free PMC Article

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