[Correlated analysis of 5 fluorouracil metabolic enzymes with tumor response after SOX regimen neoadjuvant chemotherapy in advanced gastric cancer].
OBJECTIVE
To analyze the impact of mRNA expression of oral fluoropyrimidine (S-1) metabolism on treatment outcomes in locally advanced gastric cancer patients on preoperative S-1 oxaliplatin-based chemotherapy.


METHODS
Between June 2012 and March 2013, 32 patients with preoperative AJCC stage II-III gastric cancer patients were enrolled. They received S-1 (80 mg·m⁻² × d⁻¹, days 1-14) and oxaliplatin (130 mg/m², day 1) every 3 weeks and subsequently underwent gastrectomy with D2 lymphadenectomy. Paired tumor and normal fresh frozen tissues were collected to evaluate the mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and OPRT with quantitative reverse transcription(RT) -PCR.


RESULTS
Among them, 21 (65.6%) patients had clinical tumor response and histological response occurred in 10 (31.3%) patients. Quantitative RT-PCR results showed that OPRT mRNA expression was significantly higher in clinical tumor responders than non-responders (3.95 ± 0.81 vs 1.79 ± 0.64, P = 0.005). Diffuse-type gastric cancer patients (n = 22) demonstrated higher OPRT expression levels than intestinal-type(n = 10) ones (2.54 ± 0.75 vs 1.49 ± 0.56, P = 0.014). The mRNA expressions of TS and TP in gastric cancer tissues with lymph node (LN) metastasis (n = 13) were significantly higher than those in gastric cancer tissues without LN metastasis (n = 19, both P < 0.05) .Similar results were not found for comparing dihydropyrimidine dehydrogenase expression levels (all P > 0.05).


CONCLUSIONS
OPRT, TS and TP may become potential predictive biomarkers in advanced gastric cancer patients on oral fluoropyrimidine (S-1)-based chemotherapy.
Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
Tao
T
Li
Meixia
M
Liang
Jing
J
Yuan
Xu
X
Guo
Daofu
D
Feng
Ting
T
Li
Da
D
Teng
Zheng
Z
Peng
Xin
X
Wu
Zexue
Z
Li
Hua
H
Wang
Email: chenlinbj@vip.sina.com.
Lin
L
Chen
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome
D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil