Identification of genes with differential expression in acquired drug-resistant gastric cancer cells using high-density oligonucleotide microarrays

Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):272-84. doi: 10.1158/1078-0432.ccr-1025-3.


Purpose: A major obstacle in chemotherapy is treatment failure due to anticancer drug resistance. The emergence of acquired resistance results from host factors and genetic or epigenetic changes in the cancer cells. The purpose of this study was to identify differentially expressed genes associated with acquisition of resistance in human gastric cancer cells.

Experimental design: We performed global gene expression analysis in the acquired drug-resistant gastric cancer cell lines to the commonly used drugs 5-fluorouracil, doxorubicin, and cisplatin using Affymetrix HG-U133A microarray. The gene expression patterns of 10 chemoresistant gastric cancer cell lines were compared with those of four parent cell lines using fold-change and Wilcoxon's test for data analysis.

Results: We identified over 250 genes differentially expressed in 5-fluorouracil-, cisplatin-, or doxorubicin-resistant gastric cancer cell lines. Our expression analysis also identified eight multidrug resistance candidate genes that were associated with resistance to two or more of the tested chemotherapeutic agents. Among these, midkine (MDK), a heparin-binding growth factor, was overexpressed in all drug-resistant cell lines, strongly suggesting that MDK might contribute to multidrug resistance in gastric cancer cells.

Conclusions: Our investigation provides comprehensive gene information associated with acquired resistance to anticancer drugs in gastric cancer cells and a basis for additional functional studies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cisplatin / pharmacology
  • Cytokines*
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm*
  • Fluorouracil / pharmacology
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Midkine
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Carrier Proteins
  • Cytokines
  • Neoplasm Proteins
  • Midkine
  • Doxorubicin
  • Cisplatin
  • Fluorouracil