Abstract
5-Fluorouracil (5-FU) is the most widely used anticancer agent for gastrointestinal cancers. Because many tumors show primary resistance, it is clinically meaningful to predict tumor sensitivity to the drug before treatment. cDNA microarrays containing 21,168 clones were used to identify genes associated with sensitivity to 5-FU. Gene expression profiling of 3 colorectal cancer cell lines (DLD-1, HT-29 and NUGC-3) and the corresponding 5-FU-resistant sublines (DLD-1/FU, HT-29/FU and NUGC-3/5FU/L) showed 81 genes that were differentially expressed. The gene set thus identified successfully predicted the sensitivities of 5 other colorectal cancer cell lines and could also separate 5-FU resistant clinical samples from sensitive ones.
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Bone Morphogenetic Proteins / genetics
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cluster Analysis
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Colorectal Neoplasms / drug therapy
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / pathology
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Drug Resistance, Neoplasm / genetics
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Drug Screening Assays, Antitumor / methods
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Fluorouracil / pharmacology*
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Gene Expression Profiling*
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Growth Differentiation Factor 15
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HT29 Cells
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Humans
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Inhibitory Concentration 50
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Membrane Proteins / genetics
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Oligonucleotide Array Sequence Analysis / methods*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptors, Eph Family
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Reproducibility of Results
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antimetabolites, Antineoplastic
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Bone Morphogenetic Proteins
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GDF15 protein, human
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Growth Differentiation Factor 15
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Membrane Proteins
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EPHB6 protein, human
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Receptor Protein-Tyrosine Kinases
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Receptors, Eph Family
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Fluorouracil