Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Anticancer Res. 2011 Nov;31(11):3843-9.
The aim of this study was to determine whether the relative mRNA expressions of the thymidylate synthase (TYMS) and the excision repair cross-complementing 1 (ERCC1) genes are associated with in vitro chemosensitivity to 5-fluorouracil (5-FU) and oxaliplatin in colorectal cancer, respectively.
This study included 67 patients with pathologic TNM stage II, III, and IV. TYMS and ERCC1 mRNA expression was determined using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The chemosensitivity was examined using an ATP-based chemotherapy response assay. A high response was defined as a response producing ≥40% reduction in ATP.
The mean level of TYMS mRNA expression in the groups with low and high response to 5-FU was 2.35×10(-3) ± 2.16×10(-3) 2(-(ΔCt)) and 4.54×10(-3) ± 2.46×10(-3) 2(-(ΔCt)), respectively. The mean level of ERCC1 mRNA expression in the groups with low and high response to oxaliplatin was 13.92×10(-3) ± 9.90×10(-3) 2(-(ΔCt)) and 23.59×10(-3) ± 5.88×10(-3) 2(-(ΔCt)), respectively. Groups with high response to 5-FU and oxaliplatin had significantly higher expression of TYMS and ERCC1 mRNA, respectively (p<0.01 and p=0.01, respectively).
High expression of TYMS and ERCC1 mRNA was associated with better in vitro chemosensitivity to 5-FU and oxaliplatin, respectively, in patients with colorectal cancer.
本研究旨在分别确定胸苷酸合成酶(TYMS)和切除修复交叉互补基因 1(ERCC1)的相对 mRNA 表达与结直肠癌对氟尿嘧啶(5-FU)和奥沙利铂的体外化疗敏感性是否相关。
本研究纳入了 67 例病理 TNM Ⅱ、Ⅲ和Ⅳ期患者。采用实时逆转录聚合酶链反应(RT-PCR)测定 TYMS 和 ERCC1 mRNA 表达。使用基于 ATP 的化疗反应测定法检测化疗敏感性。高反应定义为产生≥40%ATP 减少的反应。
5-FU 低反应和高反应组的 TYMS mRNA 表达平均水平分别为 2.35×10(-3)±2.16×10(-3)2(-(ΔCt))和 4.54×10(-3)±2.46×10(-3)2(-(ΔCt))。奥沙利铂低反应和高反应组的 ERCC1 mRNA 表达平均水平分别为 13.92×10(-3)±9.90×10(-3)2(-(ΔCt))和 23.59×10(-3)±5.88×10(-3)2(-(ΔCt))。5-FU 和奥沙利铂高反应组的 TYMS 和 ERCC1 mRNA 表达水平显著升高(p<0.01 和 p=0.01)。
结直肠癌患者 TYMS 和 ERCC1 mRNA 表达水平高与对 5-FU 和奥沙利铂的体外化疗敏感性更好相关。