Critical evaluation of p53 as a prognostic marker in ovarian cancer
Critical evaluation of p53 as a prognostic marker in ovarian cancer
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DOI：
10.1017/s1462399404007781
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发表时间：
2004-05-14
影响因子：
6.2
通讯作者：
Brown, Robert
中科院分区：
文献类型：
--
作者：
Hall, Jacqueline;Paul, Jim;Brown, Robert
已经从实验研究中显示了编码p53的肿瘤抑制基因在细胞对DNA损伤的反应中具有至关重要的作用。 p53在凋亡，细胞周期停滞和DNA修复中具有重要功能，这在很大程度上是由其对基因转录活性介导的。然而，尽管有大量的体外数据，但其在肿瘤如何应对化学治疗药物引起的DNA损伤方面的作用仍然存在争议。在这篇综述中，我们以卵巢癌为例，强调了p53研究作为临床结果预后标志的研究和分析的一些问题。我们旨在基于卵巢癌发表文献的知识，以确定临床研究的标准，以对p53在临床耐药性中的作用进行更确定的估计。使用关键字与布尔运营商结合使用的三个公共数据库搜索了64个临床出版物，研究了卵巢癌化疗后p53与临床结果的关系。尽管从64篇论文中的215个发表分析中，有43％报告了p53状态与与化学抗性相关的临床终点之间存在显着相关性，但只有6个分析符合最低标准，而这些分析均未发现p53与化学疗法抗性抑制端口的统计显着相关性。已发表的临床研究的结果表明，p53突变在卵巢癌中的耐药机制中的作用比体外研究所建议的要复杂。
The tumour suppressor gene encoding p53 has been shown from experimental studies to have a crucial role in how cells respond to DNA damage. p53 has important functions in apoptosis, cell-cycle arrest and DNA repair, largely mediated by its activity on gene transcription. However, despite this wealth of in vitro data, its role in how tumours respond to DNA damage induced by chemotherapeutic drugs remains controversial. In this review, we highlight some of the problems surrounding design and analysis of studies of p53 as a prognostic marker of clinical outcome, using ovarian cancer as an example. We aim to build on the knowledge of the published literature in ovarian cancer to identify criteria for clinical studies that should give a more definitive estimate of the role of p53 in clinical drug resistance. A search of three public databases using keywords combined with Boolean operators identified 64 clinical publications investigating the relationship of p53 to clinical outcome following chemotherapy in ovarian cancer. Although 43% of 215 published analyses from the 64 papers reported a significant correlation between p53 status and a clinical endpoint relevant to chemoresistance, only six analyses fulfil minimum criteria and none of these finds a statistically significant correlation of p53 with chemotherapy-resistance endpoints. The results from published clinical studies suggest a more complex role of p53 mutation in the mechanism of resistance in ovarian cancer than is suggested by in vitro studies.