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

Abstract

BackgroundHepatectomy 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.MethodsAn 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.ResultsMetastasis 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.ConclusionsThe 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 materialThe online version of this article (doi:10.1186/s13046-016-0361-8) contains supplementary material, which is available to authorized users.

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

“…The experimental protocol was approved by the Shanghai Medical Experimental Animal Care Committee. Human HCC tumor models produced by MHCC97H were established in nude mice by orthotopic inoculation, as described in our previous publications [23][24][25]. Briefly, the left lobe of the liver was exposed under anesthesia, and part of the liver surface was mechanically injured with scissors.…”

Loss of MTSS1 results in increased metastatic potential in pancreatic cancer

“…Many studies have found that loss of MTSS1 is detrimental to patient survival and prognosis [32, 33, 47–50]; however, in both colorectal and hepatocellular carcinoma, data show that elevated MTSS1 is an indicator of poor prognosis [51, 52]. Our data show that in PDAC, high MTSS1 expression is a significant predictor of better overall survival in PDAC patients.…”

Reduced Expression of Metastasis Suppressor-1 (MTSS1) Accelerates Progression of Human Bladder Uroepithelium Cell Carcinoma

“…However, there are conflicting data on whether MTSS1 expression is an indicator of good or poor prognosis in patients with advanced cancer. In hepatitis B-related hepatocellular carcinoma, elevated MTSS1 expression was found to be associated with cancer metastasis and poor prognosis (18). Up-regulation of MTSS1 expression in colorectal cancer tissues was also significantly correlated with poor differentiation, tissue invasion, high preoperative carcinoembryonic antigen level, presence of lymph node metastasis and high TNM stage (19).…”