Title: Transcription profiling of human colorectal adenocarcinoma patients after Celecoxib pre-treatment
Organism(s): Homo sapiens
Description: 23 patients. 11 received 400 mg celecoxib 2x/day for 7d prior to surgical resection of colorectal adenocarcinoma, followed by transcriptional profiling of resected tumors. (12 no-drug controls.) [original description: Pharmacological inhibition of cyclooxygenase-2 (COX-2) is being explored as a chemotherapeutic option because COX-2 protein expression is often elevated in many cancers. Cancer cells treated with COX-2 inhibitors, such as the selective COX-2 inhibitor celecoxib, show growth inhibition and the induction of apoptosis, through alterations in inflammatory processes, angiogenesis, cell adhesion and transforming growth factor beta (TGF-beta) signaling. This study was conducted to determine if the same processes are relevant to celecoxib's effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomized to receive a 7-day course of celecoxib (400 mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from patients with and without celecoxib pre-treatment. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. Of the differentially expressed genes, multiple genes involved in cellular lipid and glutathione metabolism showed decreased expression levels in celecoxib pre-treated samples; changes associated with diminished cellular proliferation. Other observed gene expression changes consistent with reduced proliferation include: altered expression of genes involved in cell adhesion (including collagen, laminin, von Willebrand factor and tenascin C), increased expression of inflammatory modulators (including interleukin-6, S100 calcium binding protein A8, and several chemokines) and decreased expression of the pro-angiogenic gene, angiogenin. Celecoxib pre-treatment for 7 days in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation. Experiment Overall Design: Patients undergoing surgical resection of histologically proven primary colorectal adenocarcinomas were consented for participation in the study. The patients enrolled in this study were randomized to receive either 400 mg celecoxib two times per day (n=11) or no COX-2 inhibitor (n=12) for 7 days prior to surgical resection. Total RNA (5 ug) from each sample was converted to double stranded cDNA using a dT-T7 promoter primer. The double stranded cDNA was then used as a template to synthesize biotinylated RNA, which was fragmented and hybridized to the Affymetrix HG_U95av2 microarray chip using Affymetrix's labeling and hybridization protocol. Experiment Overall Design: The array data was imported into GeneSpring GX 7.3 using the GC-RMA file preprocessor. The data was normalized by: (1) setting all expression measurements <0.01 to 0.01, (2) a per chip normalization to the 50th percentile, and (3) a per gene normalization to the median value across all chips.]
Design(s): unknown_experiment_design_type, transcription profiling by array
Experimental factor(s):
NSAID dosage
2 recorded
0 mg BID x 7d pre-resection 400 mg BID x 7d pre-resection
tumor site
6 recorded
ascending colon cecum colon sigmoideum Hepatic Flexure descending colon Rectosigmoid Colon
NSAID treatment
2 recorded
control condition celecoxib
tumor type
6 recorded
ascending colon cancer cecum cancer sigmoid colon cancer hepatic flexure cancer descending colon cancer rectosigmoid cancer
Publication(s): James Todd Auman, Robert Church, Soo-Youn Lee, Mark A Watson, James W Fleshman, Howard L McLeod
Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation. PubMed:18653328

Sample attribute(s):
Pathological M
2 recorded
1 0
Material Type
2 recorded
synthetic_RNA total_RNA
Pathological N
3 recorded
1 0 2
patient number
23 recorded
4865 4864 4863 4866 4874 4879 4877 4882 4861 4859 4881 4870 4871 4872 4875 4868 4867 4880 4858 4862 4860 4873 4876
2 recorded
male female
AJCC Stage
4 recorded
tumor tissue type
1 recorded
Tumor Grade
4 recorded
moderate well poor moderate to poor
1 recorded
1 recorded
Homo sapiens
Pathological T
4 recorded
4 3 1 2
Contact(s): James Todd Auman
Release Date: 10/25/2008
Submission Date:
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Assay Downloads
transcription profiling using DNA microarray
23 assays