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

 Jeung, Hei-Cheula,b,c  ;  Rha, Sun Younga,b,c  ;  Chung, Hyun Cheola,  ;  Noh, Sung Hoond  ;  Roh, Jae Kyunga,b,c  ;  Lim, Seung Joonb  ;  Shin, Sang Joona,c 
 Anti-Cancer Drugs, Vol.22(8) : 801-810, 2011 
Journal Title
 Anti-Cancer Drugs 
Issue Date
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.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
노성훈(Noh, Sung Hoon) ; 노재경(Roh, Jae Kyung) ; 라선영(Rha, Sun Young) ; 신상준(Shin, Sang Joon) ; 정현철(Chung, Hyun Cheol) ; 정희철(Jeung, Hei Cheul)
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