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

Kazuhiro Suganuma, Tetsuro Kubota, Yoshiro Saikawa, Sadanori Abe, Yoshihide Otani, Toshiharu Furukawa, Koichiro Kumai, Hirotoshi Hasegawa, Masahiko Watanabe, Masaki Kitajima, Hironobu Nakayama, Hisafumi Okabe

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Abstract

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 cyclooxygenase-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.

Original languageEnglish
Pages (from-to)355-359
Number of pages5
JournalCancer science
Volume94
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Suganuma, K., Kubota, T., Saikawa, Y., Abe, S., Otani, Y., Furukawa, T., Kumai, K., Hasegawa, H., Watanabe, M., Kitajima, M., Nakayama, H., & Okabe, H. (2003). Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray. Cancer science, 94(4), 355-359. https://doi.org/10.1111/j.1349-7006.2003.tb01446.x