晚期肺腺癌组织中TYMS基因表达水平判定及其临床意义验证

Evaluation of TYMS gene expression level and its clinical significance in advanced lung adenocarcinoma

目的确定用于TYMS基因表达水平判定的临界值,并对TYMS基因表达水平判定方法的临床指导意义进行验证。方法通过实时荧光定量PCR技术平台及2-ΔCt法计算TYMS基因相对于内参基因的表达量。将中位值作为判定TYMS基因表达水平的临界值,并通过患者接受培美曲塞化疗的短期、长期疗效对该临界值进行验证。结果在150例FFPE样本中,TYMS基因、内参基因同时可检出的检出率为89.3%,TYMS基因相对表达量在晚期肺腺癌患者不同年龄组中差异有统计学意义(P=0.025),但与患者性别、癌症分型、分期及吸烟史差异均无统计学意义。TYMS基因高表达、低表达患者在接受培美曲塞化疗后的客观有效率分别为9.8%、35.4%(P<0.05)。TYMS基因高表达、低表达患者接受培美曲塞化疗的中位无进展生存时间差异有统计学意义,分别为2.1个月、4.9个月(P=0.047);TYMS基因高表达、低表达患者中位总体生存时间差异有统计学意义,分别为9.1个月、16.7个月(P=0.024)。结论 TYMS基因表达水平判定方法适用于判定晚期肺腺癌FFPE样本中TYMS基因表达水平等级,有利于TYMS基因表达量检测的标准化,且该方法可用来预测培美曲塞化疗的疗效。

Objective To examine the relative expression of TYMS gene in 150 FFPE samples of advanced lung adenocarcino- ma patients and to validate the method for differentiating TYMS gene expression levels in term of clinical significance. Methods Real time quantitative PCR and method was used to detect the expression of TYMS and internal reference gene. The median value was used as the cut-off value and retrospective validation was performed including the short and long term therapeutic response towards pem- etrexed based chemotherapy. Results In the 150 samples we examined, the detection rate was 89.3% when both the TYMS and the internal reference gene were successfully amplified. TYMS expression was significantly correlated with late stage adenocarcinoma pa- tients＇ age groups （ P = 0. 025 ） but not significantly correlated with patients＇ gender, histology, stage or smoking history （ P 〉 0.05 ）. The ORR （ objective response rate） in TYMS high and low expression groups was 9.8% and 35.4%, respectively （ P 〈 O. 05 ）. The median progression free survival time in TYMS high and low expression group was 2.1 and 4.9 months, respectively （ P = 0.047 ）. The median overall survival time in TYMS high and low expression group was 9. 1 and 16.7 months, respectively （ P = 0. 024 ）. Conclusions The method for differentiating TYMS gene expression levels in the present study is suitable in late stage adenocarcinoma patients and sheds light on the standardization of TYMS expression detection. This method can also be used to predict the therapeutic efficiency of pemetrexed chemotherapy.