Gene Expression Profiles for Predicting the Efficacy of the Anticancer Drug 5-Fluorouracil in Breast Cancer

School of Medical and Health Science, Fooyin University, Kaohsiung, Taiwan.
DNA and cell biology (Impact Factor: 2.06). 06/2010; 29(6):285-93. DOI: 10.1089/dna.2009.1006
Source: PubMed


Chemotherapy is an important postsurgery adjuvant therapy in the treatment of breast cancer. However, because of the individual genotype differences of patients, the drug efficacy differs from person to person, even when the same chemotherapy drug is administered. The purpose of this research was to probe the gene expression profiles to predict the efficacy of 5-fluorouracil (5-FU), the common drug used in chemotherapy for various type of cancers, in Taiwanese breast cancer patients. Microarray analysis was conducted on the cancer cell line ZR-75-1 with and without 5-FU stimulation to identify the differentially expressed genes. The significant overexpressed gene groups were selected after bioinformatics software analysis to explore the molecular mechanism of 5-FU. Six strains of breast cancer cell line purchased from American Type Culture Collection were used to analyze the expression profiles of the above target gene groups. IL18, CCL28, CXCL2, SOD1, HRAS, FDXR, and CHI3L1 genes were significantly differentially expressed in 5-FU responder and nonresponder cell lines. The selected gene groups were validated with 20 strains of breast cancer primary cultures established previously in our laboratory. The experimental results demonstrated that FAM46A, IL18, CCL28, TNF, CXCL2, PLEKHA8, HRAS, FDXR, and CHI3L1 genes showed statistically significant differential expression between primary breast cancer culture cells that respond and nonrespond to 5-FU. Six genes, IL18, CCL28, CXCL2, HRAS, FDXR, and CHI3L1, showed significant differential expression pattern in both American Type Culture Collection and primary breast cancer cultured cells. The findings of this study may serve as basis for predicting the effectiveness of 5-FU on breast cancer.

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    • "Microarray-based gene expression patterns have been used to predict the clinical outcome and prognosis of patients undergoing 5-FU therapy [28]-[30]. It has also been applied to predict the therapeutic efficacy of 5-FU and to identify the biomarkers in various cancers [31], [32]. We used microarray tool for the first time to identify the key molecule involved in the 5-FU-caused intestinal injury in this study. "
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