首页> 美国卫生研究院文献>Oncology Letters >Thymidylate synthase and thymidine phosphorylase mRNA expression in primary lesions using laser capture microdissection is useful for prediction of the efficacy of FOLFOX treatment in colorectal cancer patients with liver metastasis
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Thymidylate synthase and thymidine phosphorylase mRNA expression in primary lesions using laser capture microdissection is useful for prediction of the efficacy of FOLFOX treatment in colorectal cancer patients with liver metastasis

机译:激光捕获显微切割术在原发灶中的胸苷酸合酶和胸苷磷酸化酶mRNA表达可用于预测FOLFOX治疗结直肠癌肝转移患者的疗效

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摘要

Chemotherapy with FOLFOX, which is a combination of 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin, has been used worldwide for the treatment of metastatic colorectal cancer patients. The aim of this study was to examine the candidates for predictors of the efficacy of the FOLFOX treatment regimen in colorectal cancer patients with liver metastasis, using formalin-fixed paraffin-embedded specimens. We investigated the mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT) and excision repair cross-complementing 1 (ERCC1) in 70 primary lesions and 30 liver metastatic lesions of colorectal cancer patients, using laser capture microdissection and real-time PCR methods. We then analyzed the correlation between their expression in primary lesions and those in corresponding liver metastatic lesions (n=30) and the relationship between their expression in the primary lesions and the efficacy of mFOLFOX6 in 45 colorectal cancer patients with unresectable liver metastasis. The gene expression in primary lesions positively correlated with those in corresponding liver metastatic lesions. The profiles of gene expression of primary lesions strongly correlated with those of synchronous liver metastatic lesions compared to that of metachronous liver metastatic lesions. TS and TP mRNA levels in the patients with complete response, partial response or stable disease (n=34) were significantly lower compared to those in the patients with progressive disease (n=11) (p=0.017 and p=0.04, respectively). Our results indicated that TS and TP mRNA expression profiles in primary lesions are sufficient to estimate the mRNA expression profiles in synchronous liver metastatic lesions compared to metachronous liver metastatic lesions. Additionally, these profiles may be useful predictors in the identification of eligible colorectal cancer patients with liver metastasis for FOLFOX treatment.
机译:FOLFOX的化学疗法是5-氟尿嘧啶(5-FU)/亚叶酸(LV)和奥沙利铂的组合,已在世界范围内用于治疗转移性结直肠癌患者。这项研究的目的是使用福尔马林固定石蜡包埋的标本,检查FOLFOX治疗方案对结直肠癌伴肝转移的患者疗效的预测指标。我们调查了70个大肠癌和30个大肠癌肝转移病灶中的胸苷酸合酶(TS),胸苷磷酸化酶(TP),二氢嘧啶脱氢酶(DPD),乳清酸盐磷酸核糖基转移酶(OPRT)和切除修复交叉互补1(ERCC1)的mRNA水平。癌症患者,使用激光捕获显微切割和实时PCR方法。然后,我们分析了45例无法切除的大肠癌肝转移患者在原发灶和相应肝转移灶(n = 30)中它们的表达之间的相关性,以及原发灶中它们的表达与mFOLFOX6疗效之间的关系。原发灶中的基因表达与相应肝转移灶中的基因表达呈正相关。与同步肝转移灶相比,原发灶的基因表达谱与同步肝转移灶的基因表达谱高度相关。完全缓解,部分缓解或稳定疾病(n = 34)患者的TS和TP mRNA水平显着低于进行性疾病(n = 11)患者(分别为p = 0.017和p = 0.04) 。我们的结果表明,与同期肝转移灶相比,原发灶中TS和TP mRNA表达谱足以估计同步肝转移灶中的mRNA表达谱。另外,这些概况对于鉴定合格的具有肝转移灶的结直肠癌患者进行FOLFOX治疗可能是有用的预测指标。

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