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Simple combinations of 5‐FU pathway genes predict the outcome of metastatic gastric cancer patients treated by S‐1
Author(s) -
Ichikawa Wataru,
Takahashi Takehiro,
Suto Kenichi,
Shirota Yoshinori,
Nihei Zenro,
Shimizu Michio,
Sasaki Yasutsuna,
Hirayama Renzo
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22080
Subject(s) - thymidylate synthase , dihydropyrimidine dehydrogenase , thymidine phosphorylase , capecitabine , hazard ratio , cancer , medicine , oncology , cancer research , antimetabolite , univariate analysis , biology , chemotherapy , multivariate analysis , fluorouracil , colorectal cancer , confidence interval
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. © 2006 Wiley‐Liss, Inc.