Correlation between the expression levels of TS, TP, DPD and clinical outcome in patients with phase Ⅱ, Ⅲ colon cancer receiving fluorouracil-based chemotherapy

JIN Guoquan; LI Miao

doi:10.3969/j.issn.1002-7386.2017.06.001

Abstract：Objective To investigate the correlation between the expression levels of thymidylate synthase (TS),thymidine phosphorylase (TP),dihydropyrimidine dehydrogenase (DPD) and clinical outcome in patients with phase Ⅱ,Ⅲ colon cancer receiving fluorouracil-based chemotherapy.Methods One hundred and twenty patients with phase Ⅱ,Ⅲ colon cancer who received postoperative fluorouracil-based chemotherapy were enrolled in the study.Real-time quantitative PCR (RT-PCR) analysis was used to detect the expression levels of TS,TP,DPD.Morever the correlation between the expression levels and therapeutic effects of chemotherapy as well as patient~ prognosis was analyzed.Results The expression levels of TP mRNA in tumor tissues were significantly higher than those in normal tissue,however,the expression levels of DPD mRNA in tumor tissues were significantly lower than those in normal tissues (P ＜ 0.01).The correlation analysis showed that there was a weak positive correlation between TS and TP and between DPD and TP (r 2 =0.04937,P ＜ 0.01;r 2 =0.08345,P ＜0.01).The high expressions of TS,TP mRNA were more inclined to be insensitive to 5-Fu chemotherapy and disease free survival and overall survival rates were lower (P ＜ 0.01).The multivariate COX regression analysis showed that in addition to traditional risk factors including tumor differentiation and tumor cell metastasis,the expressions of TS and TP mRNA were also independent risk factors influncing colon cancer overall survival ratea (OR =2.036,95％ C.I.:1.896 ～ 3.656;OR =2.426,95％ C.I.:2.037 ～ 2.945).Conclusion The high expressions of TS,TP are more more inclined to be insensitive to 5-Fu chemotherapy,with poor prognosis in patients with phase Ⅱ,Ⅲ colon cancer,thus,the expressions of TS and TP have certain instructive value for instituting individualized chemotherapy scheme in clinical practice.