Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer

Hei Cheul Jeung, Sun Young Rha, Sang Joon Shin, Seung Joon Lim, Jae Kyung Roh, Sung Hoon Noh, Hyun Cheol Chung

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Determination of significant associations between gene expression and predefined endpoints might improve treatment tailoring for advanced gastric cancer. We investigated the mRNA expression of 5-fluorouracil (5-FU) pathway genes in prechemotherapeutic tumor samples of primary gastric cancer to try to predict the treatment outcome of S-1 monotherapy. 5-FU pathway genes, dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS), and thymidine phosphorylase (TP), were analyzed using quantitative real-time PCR of RNA extracted from archived formalin-fixed paraffin-embedded tissues. We selected the median value for each gene as a cutoff to separate patients into high and low gene expression groups. High OPRT gene expression was significantly associated with tumor response (P=0.014). In a combined analysis including OPRT, patients with high OPRT and TP showed a higher overall response rate than did the remaining patients (40 vs. 10%, respectively; P=0.002). For survival, patients with high OPRT and low TS levels showed prolonged survival in both progression-free survival (3.4 vs. 2.4 months, P=0.024) and overall survival (11.0 vs. 8.2 months, P=0.007). In a multivariate analysis, the combinations of OPRT and TP for response and OPRT and TS for both progression-free survival and overall survival were independent variables. To conclude, mRNA expression levels of molecular markers in formalin-fixed paraffin-embedded specimens of primary gastric tumors can be useful for identifying patients with advanced gastric cancer who would most likely benefit from S-1 treatment.

Original languageEnglish
Pages (from-to)801-810
Number of pages10
JournalAnti-Cancer Drugs
Volume22
Issue number8
DOIs
Publication statusPublished - 2011 Sep

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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