Detection of biomarkers for hepatocellular carcinoma using a hybrid univariate gene selection methods

Theor Biol Med Model. 2012 Aug 6;9:34. doi: 10.1186/1742-4682-9-34.


Background: Discovering new biomarkers has a great role in improving early diagnosis of Hepatocellular carcinoma (HCC). The experimental determination of biomarkers needs a lot of time and money. This motivates this work to use in-silico prediction of biomarkers to reduce the number of experiments required for detecting new ones. This is achieved by extracting the most representative genes in microarrays of HCC.

Results: In this work, we provide a method for extracting the differential expressed genes, up regulated ones, that can be considered candidate biomarkers in high throughput microarrays of HCC. We examine the power of several gene selection methods (such as Pearson's correlation coefficient, Cosine coefficient, Euclidean distance, Mutual information and Entropy with different estimators) in selecting informative genes. A biological interpretation of the highly ranked genes is done using KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, ENTREZ and DAVID (Database for Annotation, Visualization, and Integrated Discovery) databases. The top ten genes selected using Pearson's correlation coefficient and Cosine coefficient contained six genes that have been implicated in cancer (often multiple cancers) genesis in previous studies. A fewer number of genes were obtained by the other methods (4 genes using Mutual information, 3 genes using Euclidean distance and only one gene using Entropy). A better result was obtained by the utilization of a hybrid approach based on intersecting the highly ranked genes in the output of all investigated methods. This hybrid combination yielded seven genes (2 genes for HCC and 5 genes in different types of cancer) in the top ten genes of the list of intersected genes.

Conclusions: To strengthen the effectiveness of the univariate selection methods, we propose a hybrid approach by intersecting several of these methods in a cascaded manner. This approach surpasses all of univariate selection methods when used individually according to biological interpretation and the examination of gene expression signal profiles.

MeSH terms

  • Artificial Intelligence
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Data Mining
  • Databases, Genetic / statistics & numerical data
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Liver Neoplasms / genetics*
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes*
  • Up-Regulation


  • Biomarkers, Tumor