title: Simple combinations of 5-FU pathway genes predict the outcome of metastatic gastric cancer patients treated by S-1.
abstract: We evaluated the expression of 5-FU pathway genes in prechemotherapeutic fresh frozen samples obtained from primary tumors to predict response and survival of 59 metastatic gastric cancer patients treated with S-1 monotherapy as first line treatment. Five 5-FU pathway genes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP) and uridine phosphorylase (UP), were analyzed by the quantitative real-time reverse transcriptional PCR method. Median values of each gene were selected for cut-off values separating high and low gene expressions. In univariate analyses, low TS, high OPRT and low TP were significantly associated with a tumor shrinkage and a long survival, whereas DPD and UP gene expressions did not correlate with response and survival. Multivariate analyses revealed that independent variables were OPRT and TS for response and TS and TP for survival. When OPRT and TS were combined, a significantly increased accuracy rate of 91.5% was seen for response. Similarly, an increased hazard ratio of 10.29 was observed for survival in patients possessing low TS and low TP, compared with those with high TS or high TP. The simple combinations of 2 genes, OPRT and TS for response and TS and TP for survival, may allow identification of gastric cancer patients who will benefit from S-1 chemotherapy.
authors.affiliation: Department of General and Digestive Surgery, Saitama Medical School, Iruma, Saitama, Japan. wataru@saitama-med.ac.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shirota
authors.forename: Zenro
authors.initials: Z
authors.lastname: Nihei
authors.forename: Michio
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Renzo
authors.initials: R
authors.lastname: Hirayama
mesh_terms: D000328:Adult; D000368:Aged; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010094:Oxonic Acid / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil