Colorectal Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colorectal Cancer, including details on symptoms, genetics, screening, treatment, information.

Identification of consensus genes and key regulatory elements in 5-fluorouracil resistance in gastric and colon cancer.

Szöke D, Györffy A, Surowiak P, Tulassay Z, Dietel M, Györffy B

Semmelweis University Budapest, 1st Dept. of Pediatrics, Budapest, Hungary.

BACKGROUND: 5-fluorouracil (5-FU) is widely used in the treatment of gastric and colorectal cancer. Recent microrarray studies associated different gene lists with 5-FU resistance. A major challenge in the genomic era is to find the most validated genes, and to decipher the regulatory networks responsible for the expression changes in a set of co-regulated transcripts. Our aim was to find genes repeatedly associated with 5-FU resistance, and to identify transcription factors (TFs) having overrepresented binding sites (TFBSs) in the promoter regions of genes associated with 5-FU resistance. MATERIALS AND METHODS: The analyzed data originated from 5 different publications describing genome-wide gene expression patterns associated with 5- FU resistance in gastric and colorectal cancer. First, a data warehouse containing all genes associated with resistance was set up. 39 genes were identified which were repeatedly associated with resistance. Of these, using the EZ-Retrieve web service, proximal promoter sequences were available for 33 genes. The MotifScanner software was used to detect TFBSs in this set of sequences. RESULTS: A total of 200 different TFBSs were identified. Using the statistics tool of the Java program TOUCAN, 4 binding sites were found to be significantly overrepresented: NFKappaB50 (p = 0.01), EGR2 (p = 0.027), EGR3 (p = 0.007), and NGFIC (or EGR4) (p = 0.001). These genes intercept apoptotic pathways at multiple locations in the tumor cells. CONCLUSION: We identified a consensus gene list associated with 5-FU resistance, performed an in silico comparative promoter analysis, and highlighted the potential implication of some TFs in the development of chemoresistance.

Published 12 September 2007 in Onkologie, 30(8): 421-6.
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