Molecular Features of non-B, non-C Hepatocellular Carcinoma: A PCR-array Gene Expression Profiling Study

J Hepatol. 2003 Dec;39(6):1004-12. doi: 10.1016/s0168-8278(03)00473-2.


Background/aims: Hepatocellular carcinoma (HCC) usually develops following chronic liver inflammation caused by hepatitis C or B virus. Through expression profiling in a rare type of HCC, for which the causes are unknown, we sought to find key genes responsible for each step of hepatocarcinogenesis in the absence of viral influence.

Methods: We used 68 non-B, non-C liver tissues (20 HCC, 17 non-tumor, 31 normal liver) for expression profiling with PCR-array carrying 3072 genes known to be expressed in liver tissues. To select the differentially expressed genes, we performed random permutation testing. A weighted voting classification algorithm was used to confirm the reliability of gene selection. We then compared these genes with the results of previous expression profiling studies.

Results: A total of 220 differentially expressed genes were selected by random permutation tests. The classification accuracies using these genes were 91.8, 92.0 and 100.0% by a leave-one-out cross-validation, an additional PCR-array dataset and a Stanford DNA microarray dataset, respectively. By comparing our results with previous reports on virus-infected HCC, four genes (ALB, A2M, ECHS1 and IGFBP3) were commonly selected in some studies.

Conclusions: The 220 differentially expressed genes selected by PCR-array are potentially responsible for hepatocarcinogenesis in the absence of viral influence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Algorithms
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Profiling / standards
  • Gene Expression Regulation, Neoplastic
  • Hepatitis E / complications
  • Hepatitis E / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Reproducibility of Results