Running Title: Cellular Pathways in Cancer Can we identify of Cellular Pathways Implicated in Cancer using Gene Expression Data?

The cancer state of a cell is characterized by alterations of important cellular processes such as cell proliferation, apoptosis, DNA-damage repair, etc. Some of these alterations involve modifications of the expression of genes that participate in the pathways responsible for these processes. From this simple observation it follows that the expression of genes associated with cancer related pathways should exhibit differences between the normal and the cancerous states. We explore various means to find those differences. Interestingly, these differences can only be identified when groups of genes, as opposed to isolated genes, are considered. Instead of using all the individual genes on a DNA array in comparing cohorts of cancer patients with control subjects, our analysis searches for signals within small subsets of genes that are associated with specific pathways, thereby substantially increasing the sensitivity of the analysis, while preserving the biological information contained in the pathways. We analyze 6 different pathways (p53, Ras, Brca, DNA damage repair, NFκb and β-catenin) and 4 different types of cancer: colon, pancreas, prostate and kidney. Our results are found to be mostly consistent with existing knowledge of the involvement of these pathways in different cancers. Our analysis constitutes proof of principle that it may be possible to predict the involvement of a particular pathway in cancer or other diseases by using gene expression data. Such method would be particularly useful for the types of diseases where biology is poorly understood.