进展期胃癌术后化疗效果与5-氟尿嘧啶通道基因的关系

Relationship between the fluorouracil pathway gene and effect of chemotherapy in advanced gastric cancer after surgery

目的研究进展期胃癌术后化疗效果与5-氟尿嘧啶（5-Fu）通道基因的关系。方法收集52例进展期胃癌术后辅助FOLFOX4化疗6个周期病例，建立数据库。选择5-Fu通道基因中的胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）、乳清酸磷酸核糖转移酶（OPRT）3个基因，采用反转录聚合酶链反应（RT-PCR）方法检测52例胃癌组织和临近正常组织TS、DPD、OPRTmRNA表达，探讨5．Fu通道基因对化疗效果的影响。结果肿瘤组织中相对于GAPDH，TSmRNA相对表达量为0．92±0．28，较对应正常组织中的0．71±0．30高（t=3．730，P=0．001），胃癌组织和正常组织中OPRTmRNA呈正相关（r=0．45，P=0．001），Ts和DPDmRNA表达分别在肿瘤和正常组织中无相关性；肿瘤组织和正常组织中OPRT mRNA高表达者有较长生存期（t=3．036，P=0．003；t=2．713，P=0．009），肿瘤组织低DPD mRNA表达者有较长生存期（t=2．708，P=0．009），在正常组织中，高DPDmRNA表达者有较长生存期（t=2．616，P=0．012）。结论进展期胃癌术后化疗效果与DPD和OPRT相关，与TS的表达无关。

Objective To investigate the relationship between the fluorouracil pathway gene and effect of chemotherapy in advanced gastric cancer after surgery. Methods 52 postoperative patients with advanced gastric cancer using FOLFOX4 6-cycles combined chemotherapy were collected to set up the database. The expression of thymidine synthase（TS）, dihydropyrimidine dehydrogenase（DPD） and orotate phosphoribosyltransferase（OPRT） in tumor tissue and adjacent non-tumor tissue of 52 patients with advanced gastric cancer were measured by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The influence of fluorouracil pathway gene on chemotherapy was investigated. Results The TS-mRNA level in tumor tissue was significantly higher than non-tumor tissue （0.92±0.28 vs 0.71±0.30） （t=3.730, P=0.001）. OPRT-mRNA level in tumor tissue was positively correlated with the non-tumor tissue （r=0.45, P=0.001）. No correlations were observed among other gene expressions. Patients whose high OPRT-mRNA gene expression in their tumors and non-tumor tissue showed an obviously better survival （t = 3.036, P =0.003; t = 2.713, P =0.009）. Patients with low DPD-mRNA gene expression survived longer than those with high DPD-mRNA gene expression in tumor tissue with statistical signifieance（t = 2.708, P =0.009）, whereas prolonged survival was observed in patients with high DPD-mRNA gene expression in non-tumor tissue （t = 2.616, P =0.012）. Conclusion There is close relationships between chemotherapy in advanced gastric cancer and the expression of DPD-mRNA, OPRT-mRNA; while the expression of TS-mRNA have no relation with the survival time.