Abstract
Multiple recent studies have demonstrated that colorectal cancer (CRC) is immunogenic and that host adaptive immunity (especially by CD4+ T cells) may play a role in inhibiting disease relapse or progression. We have shown that overexpressed tumor associated proteins, those abundant in the cancer state but expressed at basal levels in normal cells, can be immunogenic. The purpose of this study was to identify genes overexpressed in colorectal adenoma that maintain upregulation in CRC using publicly available microarray datasets in the NCBI Gene Expression Omnibus (GEO). Such genes may encode proteins that could be suitable as immunologic targets for a CRC vaccine. We identified 7 high quality datasets from 5 experiments (GSE 867, 4183, 1095, 5206, 15960) where human pre-malignant or cancerous tissue (3 adenoma and 4 CRC) was directly compared to normal colon. Inclusion criteria for the datasets included: commercial microarray platforms (Illumina or Affymetrix), primary tissue, normal colon expression included, data generated after 2005, and access to microarray raw data. We identified 100 genes that were at least 2-fold upregulated in both adenomas and CRC, relative to normal colon. We further characterized and ranked these genes by assigning numerical values to the following criteria: 1) strong expression in CRC as compared to normal colon at both the RNA and protein level, 2) evidence that the gene is biologically important in CRC initiation or progression, 3) limited gene expression in normal tissues, and 4) proven immunogenicity of the encoded protein. These analyses identified 83 candidate targets. We hypothesized that genes highly conserved across species would potentially have greater biologic relevance, so we analyzed relevant microarray studies in mouse CRC models (GSE 422, 784). We identified 226 murine genes upregulated in adenoma and CRC. Comparison of the human and rodent data sets revealed an overlap of 10 genes. We conclude that there are a limited number of genes upregulated in adenoma and CRC and conserved across disease in mouse and man. If these proteins are immunogenic, they may serve as novel immunologic targets to prevent the progression from normal colonic epithelium to adenoma or carcinoma.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A33.
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