Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
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DOI：
10.1038/sj.bjc.6605817
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发表时间：
2010-08-24
影响因子：
8.8
通讯作者：
Cree, I. A.
中科院分区：
文献类型：
--
作者：
Glaysher, S.;Gabriel, F. G.;Cree, I. A.
背景：卵巢癌对化疗的敏感性在临床和体外均表现出相当大的异质性。本研究验证了这种差异的分子基础在于这些患者肿瘤固有的已知耐药机制的假设。一系列的31个卵巢肿瘤的化疗敏感性，所有这些肿瘤以前都接受过铂类化疗，使用基于ATP的肿瘤化疗敏感性测定（ATP-TCA）进行评估，并与通过定量逆转录-聚合酶链反应（RT-PCR）测量的耐药基因表达相关。在从福尔马林固定的石蜡包埋的组织中提取mRNA之后，在TaqMan阵列中进行转录酶聚合酶链反应（qRT-PCR）。对管家基因（PBGD）的结果进行了标准化，并通过多元线性regression.RESULTS：预测多元线性回归模型推导出四个单一的药物（顺铂，吉西他滨，拓扑替康，和曲舒凡），并为顺铂+吉西他滨和曲舒凡+吉西他滨的组合。对于顺铂、吉西他滨、拓扑替康和曲舒凡+吉西他滨，获得了特别强的相关性。没有单个基因表达与ATP-TCA活性直接相关。参与DNA修复和凋亡的基因在卵巢癌中有很强的表达，一些药物泵也参与其中。结论：卵巢癌对化疗药物的敏感性与敏感和耐药机制相关基因的表达有关。英国癌症杂志（2010）103，656-662。doi：10.1038/sj.bjc.6605817 www.bjcancer.com在线发布2010年8月10日（C）2010英国癌症研究
BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours.METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression.RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin+gemcitabine and treosulfan+gemcitabine. Particularly strong correlations were obtained for cisplatin, gemcitabine, topotecan, and treosulfan+gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved.CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms. British Journal of Cancer (2010) 103, 656-662. doi:10.1038/sj.bjc.6605817 www.bjcancer.com Published online 10 August 2010 (C) 2010 Cancer Research UK