The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma

Med Oncol. 2010 Jun;27(2):255-61. doi: 10.1007/s12032-009-9201-4. Epub 2009 Mar 20.

Abstract

Objective: The mammalian target of rapamycin (mTOR) pathway, an important regulator of multiple cellular functions including proliferation, differentiation, tumorigenesis, and apoptosis, is up-regulated in many cancers. It has achieved considerable importance. This study was conducted to determine the status of the mTOR pathway in human hepatocellular carcinoma (HCC) and to investigate its relationship with the prognosis of HCC.

Methods: PTEN, pAkt, p27, and pS6 expression in cryo-sections gathered from 528 cases with HCC by the method of immunohistochemistry. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of HCC.

Results: The mTOR pathway was more significantly altered in high-grade tumors, and tumors with poor prognostic features. Especially, pAkt and cytoplasmic p27 expression showed the strongest associations with pathological parameters of HCC. Statistical analysis showed that HCC patients expressing pAkt, PTEN, cytoplasmic p27, and pS6 have different overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that tumor differentiation (P = 0.006), vascular invasion (P = 0.028), TNM stage (P = 0.005), pAkt (P = 0.021), PTEN (P = 0.003), p27 (P = 0.018) and pS6 (P = 0.002) were independent prognosis factors for HCC.

Conclusion: Expression of the mTOR pathway components, which are related with the transferability and invasive capacity of HCC cells, may be used as prognostic indicators in HCC.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / physiology*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / mortality
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / biosynthesis
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinase / biosynthesis
  • Phosphatidylinositol 3-Kinase / genetics
  • Prognosis
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Survival Rate / trends
  • TOR Serine-Threonine Kinases / biosynthesis
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / physiology*
  • Up-Regulation / genetics

Substances

  • Biomarkers, Tumor
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Phosphatidylinositol 3-Kinase
  • PTEN Phosphohydrolase
  • PTEN protein, human