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).

CONCLUSION: OPRT, TS and TP may become potential predictive biomarkers in advanced gastric cancer patients on oral fluoropyrimidine (S-1)-based chemotherapy.

Medienart:

Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:94

Enthalten in:

Zhonghua yi xue za zhi - 94(2014), 2 vom: 14. Jan., Seite 127-30

Sprache:

Chinesisch

Beteiligte Personen:

Li, Tao [VerfasserIn]
Liang, Meixia [VerfasserIn]
Yuan, Jing [VerfasserIn]
Guo, Xu [VerfasserIn]
Feng, Daofu [VerfasserIn]
Li, Ting [VerfasserIn]
Teng, Da [VerfasserIn]
Peng, Zheng [VerfasserIn]
Wu, Xin [VerfasserIn]
Li, Zexue [VerfasserIn]
Wang, Hua [VerfasserIn]
Chen, Lin [VerfasserIn]

Themen:

Dihydrouracil Dehydrogenase (NADP)
EC 1.3.1.2
EC 2.1.1.45
EC 2.4.2.10
EC 2.4.2.4
English Abstract
Fluorouracil
Journal Article
Orotate Phosphoribosyltransferase
RNA, Messenger
Thymidine Phosphorylase
Thymidylate Synthase
U3P01618RT

Anmerkungen:

Date Completed 09.02.2015

Date Revised 11.04.2014

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM237259907