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结直肠癌中 TYMS 和 ERCC1 mRNA 表达与体外化疗敏感性的关系。

Relationship between TYMS and ERCC1 mRNA expression and in vitro chemosensitivity in colorectal cancer.

机构信息

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.

出版信息

Anticancer Res. 2011 Nov;31(11):3843-9.

PMID:22110208
Abstract

AIM

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.

PATIENTS AND METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

目的

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。

患者和方法

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。

结果

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)。

结论

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。

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