TS mRNA表达与食管鳞癌患者5-FU化疗临床预后的相关研究

摘要

Objective: To investigate the correlation of the mRNA expression levels of thymidylate synthase ( TS) with clinicopathological parameters in patients with esophageal squamous cell carcinoma (ESCC) receiving 5 - Flurouracil - based chemotherapy as well as their clincal prognostic significance. Methods: The relative mRNA expression of TS to the internal reference gene (3 - actin in formalin - fixed paraffin - embeded primary esophageal cancer tumor specimens was measured using real - time quantitative reverse transcription polymerase chain reaction. And the relationship between TS levels with clinicopathological parameters and survival in patients with ESCC was studied. Results: TS expression levels were detected in all tumor specimens. The median TS gene expression level from 22 patients with ESCC was 0. 054. TS expression was not related to clinicopathological parameters in esophageal cancer. From multivariate analysis,the overall survival (OS) of patients with low TS mRNA levels was longer than those who with high TS mRNA levels when all patients treated with 5 - Flurouracil — Based chemotherapy (P =0. 017). Conclusion: It was suggested that intratumoral TS mRNA expression level, not associated with clinicopathological parme-ters, might is a predictive marker of survival of 5 —Flurouracil — based chemotherapy in ESCC patients. In addition , it could provide critical information for planning personalized chemotherapy .%目的:探讨食管鳞癌石蜡包埋组织中胸腺嘧啶核苷酸合成酶基因( thymidylate synthase,TS) mRNA表达水平与接受氟尿嘧啶(Fluorouracil,5-FU)化疗的患者临床病理的关系及其预后意义.方法:采用实时荧光定量RT-PCR检测22例福尔马林固定-石蜡包埋食管鳞癌组织TS mRNA的表达水平,并比较其表达水平与接受5-FU化疗的患者的临床病理及生存期之间的关系.结果:TS mRNA的表达水平与患者年龄、性别、肿瘤分化程度、TNM分期、是否吸烟饮酒、浸润深度、淋巴结转移、远处转移、血管侵犯以及神经累及均无显著性相关(P＞0.05).TS mRNA的表达水平与食管鳞癌肿瘤组织COX2 (P =0.419)、p53(P =0.804)、PCNA(P=0.555)、VEGF(P=0.184)、MDR(P =0.593)、EGFR(P=0.482)、SSTR2(P=0.377)的蛋白表达情况均无显著相关性.以5-FU为基础化疗的食管鳞癌患者,TS mRNA低表达者的总生存时间较TS mRNA高表达者明显延长(P=0.017).经COX多因素回归分析显示,食管鳞癌肿瘤组织中TS mRNA表达水平可以成为以5-FU为基础化疗的食管鳞癌患者独立的预测指标(P =0.029,95％ CI:1.161-16.278).结论:TS mRNA表达可能与食管鳞癌患者5-FU化疗后总生存时间(OS)呈负相关.食管鳞癌肿瘤组织中TS mR-NA表达水平可以作为预测以5-FU为基础化疗患者预后的独立指标.TS mRNA表达水平与食管鳞癌的恶性生物学行为无相关性.