Exploration of potential genomic portraits associated with intrahepatic recurrence in human hepatocellular carcinoma

Ann Surg Oncol. 2010 Dec;17(12):3145-54. doi: 10.1245/s10434-010-1150-9. Epub 2010 Jul 13.

Abstract

Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease with recognized variability in virus infection, genetic features, and clinical outcome. To date, transcriptional profilings of HCC have been used to predict recurrence or survival/prognosis. However, there remains a challenge to identify specific genomic prints associated with HCC recurrence, which could lead to novel therapies or effective treatment. Here we examine the association between biological signals and intrahepatic recurrence using global gene expression profiles and powerful analytical methods.

Materials and methods: Gene expression profiles were generated in 24 HCC patients with hepatitis B infections (B-type HCC) and 60 HCC patients with hepatitis C infections (C-type HCC). Gene set enrichment analysis (GSEA) was applied to the entire ranked gene lists related to early intrahepatic recurrence, based on "ideal discriminator method."

Results: GSEA revealed Ribosomal Proteins as a common regulatory pathway in B-type (P < .001) and C-type (P = .003) HCC recurrence. In addition, Proteasome (P < .001) and Pentose Phosphate Pathway (P = .01) were identified as specific pathways in each type of HCC recurrence, respectively.

Conclusions: Understanding these biologically common and different mechanisms related to intrahepatic recurrence in B-type and C-type HCC could be useful in the development of new therapeutic strategies in our fight against HCC.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Female
  • Gene Expression Profiling*
  • Hepacivirus / genetics
  • Hepatitis B / genetics
  • Hepatitis B / pathology
  • Hepatitis B / virology
  • Hepatitis B virus / genetics
  • Hepatitis C / genetics
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / virology
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Prognosis
  • RNA, Neoplasm / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Neoplasm