Gene expression profiles for predicting the efficacy of the anticancer drug 5-fluorouracil in breast cancer.
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.
Tsao
Der-An
DA
School of Medical and Health Science, Fooyin University, Kaohsiung, Taiwan.
Chang
Hui-Jen
HJ
Lin
Chi-Ying
CY
Hsiung
Suz-Kai
SK
Huang
Seng-Eng
SE
Ho
Shiu-Yen
SY
Chang
Ming-Sung
MS
Chiu
Hua-Hsien
HH
Chen
Yi-Fang
YF
Cheng
Tian-Lu
TL
Shiu-Ru
Lin
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D015415:Biomarkers; D005472:Fluorouracil