Expression level of thymidylate synthase is a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer

J Gastroenterol. 2005 Feb;40(2):143-7. doi: 10.1007/s00535-004-1512-9.

Abstract

Background: It is important to seek the appropriate chemotherapy drugs to effectively eliminate colorectal cancers. To avoid unnecessary medication and uncomfortable side effects, it is important to estimate the chemosensitivity of cancers to 5-fluorouracil (5-FU) before chemotherapy.

Methods: We examined thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions in 23 colorectal cancers, using quantitative reverse transcription-polymerase chain reaction (RT-PCR). We then evaluated the relationship between TS and DPD gene expression levels and the sensitivity of colorectal cancers to 5-FU, as determined by histoculture drug response assay (HDRA).

Results: A significant increase in the TS expression score was observed in 5-FU-sensitive colorectal cancers (0.57 +/- 0.19) compared to 5-FU-resistant ones (1.16 +/- 0.98; P = 0.029), whereas no significant differences in DPD expression scores were observed in 5-FU-sensitive colorectal cancers (0.86 +/- 1.19) compared to 5-FU-resistant ones (0.56 +/- 1.05; P = 0.603).

Conclusions: TS mRNA may be useful as a predictor of the 5-FU chemosensitivity of colorectal cancers.

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology*
  • Dihydrouracil Dehydrogenase (NADP)
  • Drug Screening Assays, Antitumor
  • Fluorouracil / therapeutic use*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / enzymology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidylate Synthase / metabolism*

Substances

  • Antimetabolites, Antineoplastic
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Fluorouracil