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

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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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