Simple combinations of 5-FU pathway genes predict the outcome of metastatic gastric cancer patients treated by S-1.
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.
Ichikawa
Wataru
W
Department of General and Digestive Surgery, Saitama Medical School, Iruma, Saitama, Japan. wataru@saitama-med.ac.jp
Takahashi
Takehiro
T
Suto
Kenichi
K
Shirota
Yoshinori
Y
Nihei
Zenro
Z
Shimizu
Michio
M
Sasaki
Yasutsuna
Y
Hirayama
Renzo
R
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
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil