title: Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer.
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.
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hei-Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Lim
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010094:Oxonic Acid / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013534:Survival; D005641:Tegafur / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D012333:RNA, Messenger; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil