Integrative analysis of cancer pathway progression and coherence

Abstract

We analyzed the cancer pathways in the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. The database provides a collective of signaling pathway members involved in cancer progression. However, the KEGG cancer pathways, unlike signaling pathways, have not been analyzed extensively with gene expression and mutation data. We transformed the colorectal cancer pathway into discrete X and Y scales and analyzed the relative expression levels of adenoma and carcinoma samples as well as the distribution of mutation targets. The X scale corresponds to the downstream location in a pathway, whereas the Y scale corresponds to the stage of the tumor. The gene expression values of the early stage pathway members are significantly higher than of the rest of the pathway members in colorectal adenoma tissues. The colorectal cancer pathway shows some degree of coherence in the carcinoma samples. The correlated gene pairs responsible for the coherence of the colorectal cancer pathway in the carcinoma samples are supported, in part, by the literature and may suggest novel regulatory associations. Finally, there are more mutation targets in the nucleus as well as the late tumor stages of the KEGG colorectal cancer pathway.