TY - JOUR
T1 - Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer
AU - Jeung, Hei Cheul
AU - Rha, Sun Young
AU - Shin, Sang Joon
AU - Lim, Seung Joon
AU - Roh, Jae Kyung
AU - Noh, Sung Hoon
AU - Chung, Hyun Cheol
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
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U2 - 10.1097/CAD.0b013e328345c9ae
DO - 10.1097/CAD.0b013e328345c9ae
M3 - Article
C2 - 21572321
AN - SCOPUS:80051546264
SN - 0959-4973
VL - 22
SP - 801
EP - 810
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
IS - 8
ER -
