Possible chemoresistance‐related genes for gastric cancer detected by cDNA microarray

• Published in: Cancer science Vol. 94; no. 4; pp. 355 - 359
• Main Authors: Suganuma, Kazuhiro, Kubota, Tetsuro, Saikawa, Yoshiro, Abe, Sadanori, Otani, Yoshihide, Furukawa, Toshiharu, Kumai, Koichiro, Hasegawa, Hirotoshi, Watanabe, Masahiko, Kitajima, Masaki, Nakayama, Hironobu, Okabe, Hisafumi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2003; Blackwell; John Wiley & Sons, Inc
• Subjects: 5-Fluorouracil; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer; Cell Division - drug effects; Chemoresistance; Cisplatin; Cisplatin - therapeutic use; DNA microarrays; DNA, Neoplasm - analysis; Doxorubicin; Doxorubicin - therapeutic use; Drug Resistance, Neoplasm - genetics; Epidermal growth factor; Female; Fluorouracil - therapeutic use; Formazans; Gastric cancer; Gastric Mucosa - metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; General aspects; Glutathione; Heparin; Humans; Immunoglobulins; Male; Medical sciences; Membrane permeability; Metallothionein; Middle Aged; Mitomycin - therapeutic use; Mitomycin C; Mucosa; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Pharmacology. Drug treatments; Retina; Retinoblastoma; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Tetrazolium Salts; Tumor Cells, Cultured - drug effects; Tumors; Vascular permeability factor; Antineoplastic agent; Cyclooxygenase 2; DNA chip; Epidermal growth factor; Gene; Glutathione transferase; Genetics; Gastric disease; Fluorouracil; Platinum II Complexes; Human; Stomach; Treatment resistance; Enzyme; Transferases; Fluoropyrimidine derivatives; Cytokine; Enzyme inhibitor; ); Dihydropyrimidine dehydrogenase (NADP; Malignant tumor; Thymidylate synthase; Cisplatin; Alkylating agent; Methyltransferases; Antimetabolic; Polypeptide; Analog; Digestive diseases; Pyrimidine derivatives; Oxidoreductases; Fluorine Organic compounds; Growth factor
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2003.tb01446.x

To identify chemoresistance‐related genes of gastric cancer, we utilized cDNA microarray technology. Thirty‐five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium‐based 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5‐fluorouracil (5‐FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP‐resistance‐related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma‐binding protein‐1. In addition, further selection of DDP‐resistance‐related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein‐IG and heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) were identified as candidate DDP‐resistance‐related genes. When known DDP‐resistance‐related genes were analyzed according to the MTT assay result, families of glutathione‐S‐transferase and cydooxygenase‐2 genes were also evaluated as resistance‐related genes. For 5‐FU resistance, dihydropyrimidine dehydrogenase and HB‐EGF‐like growth factor genes were also suggested to be resistance‐related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer. (Cancer Sci 2003; 94: 355–359)