Abstract C25: A five-gene signature is associated with tumor progression and poor prognosis in colorectal cancer

Abstract

Abstract In order to develop an experimentally derived molecular signature closely associated with survival of colorectal cancer (CRC) patients from mouse tumor models, we isolated single cell-derived progenies (SCPs) from SW480 CRC cell line and compared their metastatic potential in an orthotopic implantation model of murine CRC. We compared the differences in the gene expression profiles of a high metastatic variant SCP51, a low metastatic variant SCP58 and their parent SW480/EGFP. We found that 143 genes were commonly differentially expressed between SCP51 and SCP58 cells, SCP58 and SW480/EGFP. Using Gene-annotation enrichment analysis of DAVID, 80 genes were found in top ten clusters of the analysis. Thirty-two genes of above the 80-gene set were found to be involved in metastasis by Genclip, a text mining program. We selected five genes (LYN, SDCBP, MAP4K4, DKK1 and MID1) for immunohistochemical analysis in a cohort of 181 CRC patients. Results showed those LYN, SDCBP, MAP4K4, MID1 and five-gene signatures were significantly correlated with overall survival in patients with CRC. We also found that LYN, MAP4K4 and MID1 but not SDCBP and DKK1 expression was closely correlated with lymph node metastasis and Dukes classification in patients with CRC. Our five-gene signature was closerly associated with survival of CRC patients and could be used as a potential prognostic factor for CRC. Citation Information: Cancer Res 2009;69(23 Suppl):C25.