LIM and SH3 protein 1, a promoter of cell proliferation and migration, is a novel independent prognostic indicator in hepatocellular carcinoma

Eur J Cancer. 2013 Mar;49(4):974-83. doi: 10.1016/j.ejca.2012.09.032. Epub 2012 Oct 18.

Abstract

LIM and SH3 protein 1 (LASP-1) plays a significant role in the formation of several malignant tumours. However, the biological and clinical significances of LASP-1 in hepatocellular carcinoma (HCC) remain largely unknown. Using immunohistochemistry, we analysed LASP-1 expression in 144 clinicopathologically characterised HCC cases. Using gene and transfection and RNA interference, we investigated the effects of LASP-1 overexpression and depletion on tumour cellular behaviour in vitro. LASP-1 expression was detected in not only cytoplasm and but also nucleus of HCC and liver cells. The positive rates of both cytosolic and nuclear LASP-1 expression in HCC were higher than adjacent non-tumourous tissues. Statistical analysis showed that heterogeneous LASP-1 expression is associated with hepatitis B surface antigen (HBsAg) and serum alpha-fetoprotein (AFP) level of HCC patients. A significant trend was identified between cytosolic LASP-1 overexpression in HCC and worsening clinical prognosis. Multivariate survival analysis showed that cytosolic LASP-1 expression was recognised as an independent prognostic factor of patient's survival. In vitro study showed LASP-1 promoted cell proliferation and migration, and resulted in aggressive phenotypes of cancer cells. LASP-1 is a valuable marker of HCC progression. High cytosolic LASP-1 expression is associated with poor overall survival in HCC patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Case-Control Studies
  • Cell Adhesion
  • Cell Cycle
  • Cell Movement*
  • Cell Nucleus
  • Cell Proliferation*
  • Cells, Cultured
  • Cytoplasm
  • Cytoskeletal Proteins / antagonists & inhibitors
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Hepatitis B Surface Antigens / metabolism
  • Hepatocytes
  • Humans
  • Immunoenzyme Techniques
  • LIM Domain Proteins / antagonists & inhibitors
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Small Interfering / genetics
  • Survival Rate

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Hepatitis B Surface Antigens
  • LASP1 protein, human
  • LIM Domain Proteins
  • RNA, Small Interfering